Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4+ T-cell help in CD8+ T-cell responses
Identifieur interne : 000223 ( Istex/Corpus ); précédent : 000222; suivant : 000224Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4+ T-cell help in CD8+ T-cell responses
Auteurs : Yan Wu ; Yang LiuSource :
- Current Biology [ 0960-9822 ] ; 1994.
English descriptors
- Teeft :
- Accessory cells, Antigenpresenting cells, Antiviral cytotoxic, Cell, Cell activation, Cell density, Cell growth, Cell proliferation, Cell responses, Cells bypasses, Clonal expansion, Costimulatory activity, Ctla4, Ctla4 ligand, Current biology, Cytokine production, Cytotoxic, Cytotoxic responses, Dendritic cells decreases, Differential requirement, Flow cytometry, Functional maturation, Helper activity, Helper cell, Hybridoma supernatants, Immunol, Induction, Influenza, Influenza virus, Influenza virus subtype, Linsley, Mabs, Model system, Monoclonal, Monoclonal antibodies, Monoclonal antibody, Natural killer cells, Potent inducer, Proc natl acad, Receptor, Research paper, Spleen, Spleen accessory cells, Spleen cells, Target cells, Tumor rejection, Uninfected spleen cells, Viable cells, Viral, Viral induction, Viral infection.
Abstract
Abstract: Background: CD4+ T-cell help is critical for cytotoxic (CD8+) T-lymphocyte responses to many antigens, such as viruses, minor histocompatibility antigens and allogeneic major histocompatibility antigens. However, the nature of such help is still a mystery: cytokines such as interleukin-2 may be involved but cell–cell contact may also be necessary. As some viruses can induce CD8+ T-cell responses in the absence of CD4+ T cells, we asked whether these viruses and CD4+ T cells share a pathway for helping the CD8+ T-cell response.Results We show here that the H2N2 subtype of influenza virus, which elicits a CD4+ T-cell-independent anti-viral CD8+ T-cell response in vitro, induces expression of the co-stimulatory molecule B7-2, but not of B7, on the cell surface of antigen-presenting cells. In contrast, the H1N1 subtype of influenza virus, which requires CD4+ T-cell help to elicit CD8+ T-cell responses under the same conditions, does not induce B7-2 expression. We also find that CD4+ T cells can induce expression of B7-2 on antigen-presenting cells. In both cases, the induced B7-2 is necessary for the clonal expansion and functional maturation of CD8+ T cells.Conclusion Our results support the view that the induction of co-stimulatory activity on antigen-presenting cells by CD4+ T cells can substitute for the requirement for exogenous interleukin-2 in CD8+ T-cell help. Viruses that can induce co-stimulatory activity on antigen-presenting cells thus induce a CD4+ T-cell-independent CD8+ T-cell response. These findings could explain the reported differences in the requirements for CD4+ T cells in CD8+ T-cell responses.
Url:
DOI: 10.1016/S0960-9822(00)00110-X
Links to Exploration step
ISTEX:85C4D5CBFBBA979B81FD56C641D24C8A231154B1Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4+ T-cell help in CD8+ T-cell responses</title><author><name sortKey="Wu, Yan" sort="Wu, Yan" uniqKey="Wu Y" first="Yan" last="Wu">Yan Wu</name><affiliation><mods:affiliation>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</mods:affiliation></affiliation></author><author><name sortKey="Liu, Yang" sort="Liu, Yang" uniqKey="Liu Y" first="Yang" last="Liu">Yang Liu</name><affiliation><mods:affiliation>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:85C4D5CBFBBA979B81FD56C641D24C8A231154B1</idno><date when="1994" year="1994">1994</date><idno type="doi">10.1016/S0960-9822(00)00110-X</idno><idno type="url">https://api.istex.fr/ark:/67375/6H6-ZCTDQXX1-H/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000223</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000223</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4+ T-cell help in CD8+ T-cell responses</title><author><name sortKey="Wu, Yan" sort="Wu, Yan" uniqKey="Wu Y" first="Yan" last="Wu">Yan Wu</name><affiliation><mods:affiliation>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</mods:affiliation></affiliation></author><author><name sortKey="Liu, Yang" sort="Liu, Yang" uniqKey="Liu Y" first="Yang" last="Liu">Yang Liu</name><affiliation><mods:affiliation>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Current Biology</title><title level="j" type="abbrev">CURBIO</title><idno type="ISSN">0960-9822</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1994">1994</date><biblScope unit="volume">4</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="499">499</biblScope><biblScope unit="page" to="505">505</biblScope></imprint><idno type="ISSN">0960-9822</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0960-9822</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Accessory cells</term><term>Antigenpresenting cells</term><term>Antiviral cytotoxic</term><term>Cell</term><term>Cell activation</term><term>Cell density</term><term>Cell growth</term><term>Cell proliferation</term><term>Cell responses</term><term>Cells bypasses</term><term>Clonal expansion</term><term>Costimulatory activity</term><term>Ctla4</term><term>Ctla4 ligand</term><term>Current biology</term><term>Cytokine production</term><term>Cytotoxic</term><term>Cytotoxic responses</term><term>Dendritic cells decreases</term><term>Differential requirement</term><term>Flow cytometry</term><term>Functional maturation</term><term>Helper activity</term><term>Helper cell</term><term>Hybridoma supernatants</term><term>Immunol</term><term>Induction</term><term>Influenza</term><term>Influenza virus</term><term>Influenza virus subtype</term><term>Linsley</term><term>Mabs</term><term>Model system</term><term>Monoclonal</term><term>Monoclonal antibodies</term><term>Monoclonal antibody</term><term>Natural killer cells</term><term>Potent inducer</term><term>Proc natl acad</term><term>Receptor</term><term>Research paper</term><term>Spleen</term><term>Spleen accessory cells</term><term>Spleen cells</term><term>Target cells</term><term>Tumor rejection</term><term>Uninfected spleen cells</term><term>Viable cells</term><term>Viral</term><term>Viral induction</term><term>Viral infection</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Background: CD4+ T-cell help is critical for cytotoxic (CD8+) T-lymphocyte responses to many antigens, such as viruses, minor histocompatibility antigens and allogeneic major histocompatibility antigens. However, the nature of such help is still a mystery: cytokines such as interleukin-2 may be involved but cell–cell contact may also be necessary. As some viruses can induce CD8+ T-cell responses in the absence of CD4+ T cells, we asked whether these viruses and CD4+ T cells share a pathway for helping the CD8+ T-cell response.Results We show here that the H2N2 subtype of influenza virus, which elicits a CD4+ T-cell-independent anti-viral CD8+ T-cell response in vitro, induces expression of the co-stimulatory molecule B7-2, but not of B7, on the cell surface of antigen-presenting cells. In contrast, the H1N1 subtype of influenza virus, which requires CD4+ T-cell help to elicit CD8+ T-cell responses under the same conditions, does not induce B7-2 expression. We also find that CD4+ T cells can induce expression of B7-2 on antigen-presenting cells. In both cases, the induced B7-2 is necessary for the clonal expansion and functional maturation of CD8+ T cells.Conclusion Our results support the view that the induction of co-stimulatory activity on antigen-presenting cells by CD4+ T cells can substitute for the requirement for exogenous interleukin-2 in CD8+ T-cell help. Viruses that can induce co-stimulatory activity on antigen-presenting cells thus induce a CD4+ T-cell-independent CD8+ T-cell response. These findings could explain the reported differences in the requirements for CD4+ T cells in CD8+ T-cell responses.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>spleen cells</json:string><json:string>cytotoxic</json:string><json:string>immunol</json:string><json:string>linsley</json:string><json:string>receptor</json:string><json:string>viral</json:string><json:string>monoclonal</json:string><json:string>ctla4</json:string><json:string>mabs</json:string><json:string>spleen</json:string><json:string>viral induction</json:string><json:string>antigenpresenting cells</json:string><json:string>current biology</json:string><json:string>clonal expansion</json:string><json:string>functional maturation</json:string><json:string>monoclonal antibody</json:string><json:string>viable cells</json:string><json:string>influenza virus</json:string><json:string>research paper</json:string><json:string>flow cytometry</json:string><json:string>cell activation</json:string><json:string>costimulatory activity</json:string><json:string>proc natl acad</json:string><json:string>cytotoxic responses</json:string><json:string>antiviral cytotoxic</json:string><json:string>cell responses</json:string><json:string>cells bypasses</json:string><json:string>monoclonal antibodies</json:string><json:string>induction</json:string><json:string>influenza</json:string><json:string>cytokine production</json:string><json:string>dendritic cells decreases</json:string><json:string>target cells</json:string><json:string>tumor rejection</json:string><json:string>viral infection</json:string><json:string>natural killer cells</json:string><json:string>potent inducer</json:string><json:string>hybridoma supernatants</json:string><json:string>accessory cells</json:string><json:string>cell density</json:string><json:string>helper cell</json:string><json:string>cell proliferation</json:string><json:string>model system</json:string><json:string>helper activity</json:string><json:string>ctla4 ligand</json:string><json:string>influenza virus subtype</json:string><json:string>differential requirement</json:string><json:string>cell growth</json:string><json:string>spleen accessory cells</json:string><json:string>uninfected spleen cells</json:string><json:string>cell</json:string></teeft></keywords><author><json:item><name>Yan Wu</name><affiliations><json:string>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</json:string></affiliations></json:item><json:item><name>Yang Liu</name><affiliations><json:string>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Research Paper</value></json:item></subject><arkIstex>ark:/67375/6H6-ZCTDQXX1-H</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: Background: CD4+ T-cell help is critical for cytotoxic (CD8+) T-lymphocyte responses to many antigens, such as viruses, minor histocompatibility antigens and allogeneic major histocompatibility antigens. However, the nature of such help is still a mystery: cytokines such as interleukin-2 may be involved but cell–cell contact may also be necessary. As some viruses can induce CD8+ T-cell responses in the absence of CD4+ T cells, we asked whether these viruses and CD4+ T cells share a pathway for helping the CD8+ T-cell response.Results We show here that the H2N2 subtype of influenza virus, which elicits a CD4+ T-cell-independent anti-viral CD8+ T-cell response in vitro, induces expression of the co-stimulatory molecule B7-2, but not of B7, on the cell surface of antigen-presenting cells. In contrast, the H1N1 subtype of influenza virus, which requires CD4+ T-cell help to elicit CD8+ T-cell responses under the same conditions, does not induce B7-2 expression. We also find that CD4+ T cells can induce expression of B7-2 on antigen-presenting cells. In both cases, the induced B7-2 is necessary for the clonal expansion and functional maturation of CD8+ T cells.Conclusion Our results support the view that the induction of co-stimulatory activity on antigen-presenting cells by CD4+ T cells can substitute for the requirement for exogenous interleukin-2 in CD8+ T-cell help. Viruses that can induce co-stimulatory activity on antigen-presenting cells thus induce a CD4+ T-cell-independent CD8+ T-cell response. These findings could explain the reported differences in the requirements for CD4+ T cells in CD8+ T-cell responses.</abstract><qualityIndicators><score>9.336</score><pdfWordCount>4360</pdfWordCount><pdfCharCount>26712</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>7</pdfPageCount><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>248</abstractWordCount><abstractCharCount>1649</abstractCharCount><keywordCount>1</keywordCount></qualityIndicators><title>Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4+ T-cell help in CD8+ T-cell responses</title><pmid><json:string>7922370</json:string></pmid><pii><json:string>S0960-9822(00)00110-X</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Current Biology</title><language><json:string>unknown</json:string></language><publicationDate>1994</publicationDate><issn><json:string>0960-9822</json:string></issn><pii><json:string>S0960-9822(00)X0201-1</json:string></pii><volume>4</volume><issue>6</issue><pages><first>499</first><last>505</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1994</json:string><json:string>3-3/6.1</json:string></date><geogName></geogName><orgName><json:string>Medical Center</json:string><json:string>Kaplan Comprehensive Cancer Center</json:string><json:string>New York University</json:string><json:string>Liu RESEARCH PAPER Fig</json:string><json:string>National Institute of Health</json:string><json:string>USA</json:string></orgName><orgName_funder><json:string>National Institute of Health</json:string><json:string>USA</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Stanislav</json:string><json:string>Our</json:string><json:string>Guerder</json:string><json:string>John Hess</json:string><json:string>Victor Nussenzweig</json:string><json:string>Min Zhao</json:string><json:string>Matzinger</json:string><json:string>Data</json:string><json:string>Yang Liu</json:string><json:string>Ranheim</json:string><json:string>Kipps</json:string><json:string>Janet Orlin</json:string></persName><placeName><json:string>Chicago</json:string><json:string>York</json:string><json:string>Cambridge</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Boog et al.</json:string><json:string>[45]</json:string><json:string>[37,38]</json:string><json:string>[29]</json:string><json:string>[6]</json:string><json:string>[34-36]</json:string><json:string>[44]</json:string><json:string>[39]</json:string><json:string>[24-28]</json:string><json:string>[32]</json:string><json:string>[20-23]</json:string><json:string>[29-31]</json:string><json:string>[20]</json:string><json:string>[18,19]</json:string><json:string>[12,13]</json:string><json:string>[41]</json:string><json:string>[25]</json:string><json:string>[8-11]</json:string><json:string>[40]</json:string><json:string>[24]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-ZCTDQXX1-H</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - cell biology</json:string><json:string>2 - biochemistry & molecular biology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - developmental biology</json:string></scienceMetrix><scopus><json:string>1 - Life Sciences</json:string><json:string>2 - Agricultural and Biological Sciences</json:string><json:string>3 - General Agricultural and Biological Sciences</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - General Biochemistry, Genetics and Molecular Biology</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>1994</publicationDate><copyrightDate>1994</copyrightDate><doi><json:string>10.1016/S0960-9822(00)00110-X</json:string></doi><id>85C4D5CBFBBA979B81FD56C641D24C8A231154B1</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-ZCTDQXX1-H/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-ZCTDQXX1-H/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-ZCTDQXX1-H/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4+ T-cell help in CD8+ T-cell responses</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>©1994 Elsevier Science Ltd</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</p></availability><date>1994</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note type="content">Section title: Research Paper</note><note type="content">Figure 1: Induction of the co-stimulatory molecule B7-2 on non-T spleen cells in BALB/c ByJ mice by influenza virus. The figure shows flow-cytometry analyses of the expression on influenza virus-infected or uninfected non-T spleen cells of the surface molecules B7, B7-2, HSA and, as a control, immunoglobulin Fc receptor (FcR). T-depleted spleen cells from BALB/cByJ mice were stimulated with either H1N1 or H2N2 subtypes of influenza virus for 16 hours. The viable cells (106 per sample) were incubated with saturating amounts of monoclonal antibodies (mAbs) against B7 (3A12) [24], B7-2 (GL-1) [25], HSA (20C9) [20] and FcR (2.4G2) [44]. The binding of 20C9 and 3A12 was detected by FITC-labeled goat anti-hamster IgG, whereas the binding of 2.G2 and GL-1 was detected by FITC-labeled mouse anti-rat IgG.</note><note type="content">Figure 2: Clonal expansion and functional maturation of CD8+ T cells induced by anti-CD3 mAb and virus-infected antigen-presenting cells. (a) Proliferation of CD8+ T cells when non-T spleen cells stimulated by influenza virus strains H1N1 (PR8) or H2N2 (A/JAP) were used as antigen-presenting cells. Viable, virus-infected or uninfected non-T spleen cells were fixed and compared for their co-stimulatory activity for CD8+ T cells (5 x 104 per well), as assayed by the proliferation of CD8+ T cells in response to anti-CD3 mAb. (b) Inhibition of co-stimulatory activity by anti-B7-2 mAb (GL-1) or anti-B7 mAb (3A12). CD8+ T cells (5 x 104 per well) and fixed, A/JAP-infected non-T spleen cells (105 per well) were incubated in the presence of anti-CD3 mAb and varying concentrations of the anti-B7-2 or anti-B7 mAbs. (c) Cytotoxicity of CD8+ T cells activated by anti-CD3 mAb plus antigen-presenting cells. CD8+ T cells (3 x 106) were activated by anti-CD3 plus fixed, virus-stimulated, syngeneic antigen-presenting cells (6 x 106) for 72 hours, and the cytotoxicity determined by an anti-CD3 redirected lysis assay, using P815 cells as targets. When unstimulated or H1N1 virus-stimulated antigen-presenting cells were used, the CD8 T cell yield is 1.2 x 106, whereas when H2N2 virus-activated antigen-presenting cells were used, the CD8+ T cell yield is 6 x 106. Effector T cells are titrated to give different ratios of effector: target cells (E/T).</note><note type="content">Figure 3: Induction of co-stimulatory activity on spleen accessory cells. (a) CD4+ but not CD8+ T cells induce co-stimulatory activity on antigen-presenting cells (APCs). Aliquots of spleen cells received either one of the following treatments: complement alone (C′), anti-CD4 mAb plus complement (CD4–), anti-CD8 mAb plus complement (CD8–) or anti-CD4 plus anti-CD8 plus complement (CD4–CD8–). These preparations of spleen cells were cultured for 16 hours in the presence or absence of anti-CD3 mAb (@CD3). (b) Induction of co-stimulatory activity on antigen-presenting cells requires contact between T cells and antigen-presenting cells. Total spleen cells (upper chambers) and T-depleted cells (lower chambers) were separated by a 0.4 μm polycarbonate membrane. The cell preparations were cultured in the presence or absence of a 1:40 dilution of anti-CD3 for 16 hours and treated with anti-Thy1.2 plus complement to deplete T cells. The T-depleted cells were fixed and used as antigen-presenting cells. The proliferative responses of CD8+ T cells to added anti-CD3 mAb were measured as described in Material and methods. (c) Anti-CD3-redirected cytotoxicity of the activated CD8+ T cells. CD8+ T cells (3 x 106) stimulated by anti-CD3 plus different accessory cells (3 x 106) were incubated with 51Cr-labeled P815 cells for 6 hours, and the CD8+ T-cell activity determined by specific lysis (%). Equal fractions of viable cells recovered are used as effector cells in the two groups. As the cell yields are different, the ratios of effector: target cells (E/T) are different. When antigen-presenting cells are isolated from anti-CD3-stimulated spleen cells, the E/T ratios are 90, 30, 10, 3, 1 and 0.3; whereas when antigen-presenting cells are isolated from unstimulated spleen cells, the E/T ratios are 60, 20, 6.6, 2.2, 0.7, and 0.23.</note><note type="content">Figure 4: B7-2 and HSA, but not B7, contribute to the co-stimulatory activity on antigen-presenting cells induced by anti-CD3 activated T cells. (a) Induction of B7-2, but not B7 or HSA, by anti-CD3 activated T cells, as determined by flow cytometry using biotinylated anti-B7-2 (GL-1) [25], anti-B7 (7A5) [24], or anti-HSA (20C9) [20] mAbs. The binding of these mAbs was detected using phycoerythrin-labeled avidin. Data shown are flow cytometric profiles of T-depleted spleen cells cultured in the presence (continuous lines) or absence (dotted lines) of anti-CD3 mAb. (b) Inhibition of co-stimulatory activity by mAbs. Anti-CD3-activated spleen cells were depleted of T cells and fixed by paraformaldehyde. The fixed antigen-presenting cells and anti-CD3 mAb were used to activate CD8+ T cells purified from syngeneic spleen cells. Purified mAbs specific for B7, B7-2 and HSA were added at the beginning of the culture.</note><note type="content">Figure 5: Viral induction of co-stimulatory activity on antigen-presenting cells bypasses CD4+ T-cell help in CD8+ T-cell responses. (a) The CD4+ T-cell receptor recognizes MHC class II–peptide complexes on antigen-presenting cells; this interaction either directly or indirectly (through a CD40–CD40 ligand interaction, or through cytokine production) induces the expression of co-stimulatory activity (Cos) on antigen-presenting cells. (b) The antigen-presenting cells with the induced co-stimulatory activity can activate CD8+ T cells directly, via a receptor (Cos R) for the co-stimulatory activity. (c) Viral infection can induce co-stimulatory activity on antigen-presenting cells either directly, as shown in this report, or possibly indirectly, by inducing non-specific host responses such as activation of natural killer cells, that in turn produce interferon γ, a potent inducer of B7-2 on antigen-presenting cells. CD8+ T cells can then be activated by antigen-presenting cells in the absence of CD4+ T cells (b).</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4+ T-cell help in CD8+ T-cell responses</title><author xml:id="author-0000"><persName><forename type="first">Yan</forename><surname>Wu</surname></persName><affiliation>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Yang</forename><surname>Liu</surname></persName><note type="correspondence"><p>Corresponding author.</p></note><affiliation>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</affiliation></author><idno type="istex">85C4D5CBFBBA979B81FD56C641D24C8A231154B1</idno><idno type="ark">ark:/67375/6H6-ZCTDQXX1-H</idno><idno type="DOI">10.1016/S0960-9822(00)00110-X</idno><idno type="PII">S0960-9822(00)00110-X</idno></analytic><monogr><title level="j">Current Biology</title><title level="j" type="abbrev">CURBIO</title><idno type="pISSN">0960-9822</idno><idno type="PII">S0960-9822(00)X0201-1</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1994"></date><biblScope unit="volume">4</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="499">499</biblScope><biblScope unit="page" to="505">505</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1994</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: Background: CD4+ T-cell help is critical for cytotoxic (CD8+) T-lymphocyte responses to many antigens, such as viruses, minor histocompatibility antigens and allogeneic major histocompatibility antigens. However, the nature of such help is still a mystery: cytokines such as interleukin-2 may be involved but cell–cell contact may also be necessary. As some viruses can induce CD8+ T-cell responses in the absence of CD4+ T cells, we asked whether these viruses and CD4+ T cells share a pathway for helping the CD8+ T-cell response.Results We show here that the H2N2 subtype of influenza virus, which elicits a CD4+ T-cell-independent anti-viral CD8+ T-cell response in vitro, induces expression of the co-stimulatory molecule B7-2, but not of B7, on the cell surface of antigen-presenting cells. In contrast, the H1N1 subtype of influenza virus, which requires CD4+ T-cell help to elicit CD8+ T-cell responses under the same conditions, does not induce B7-2 expression. We also find that CD4+ T cells can induce expression of B7-2 on antigen-presenting cells. In both cases, the induced B7-2 is necessary for the clonal expansion and functional maturation of CD8+ T cells.Conclusion Our results support the view that the induction of co-stimulatory activity on antigen-presenting cells by CD4+ T cells can substitute for the requirement for exogenous interleukin-2 in CD8+ T-cell help. Viruses that can induce co-stimulatory activity on antigen-presenting cells thus induce a CD4+ T-cell-independent CD8+ T-cell response. These findings could explain the reported differences in the requirements for CD4+ T cells in CD8+ T-cell responses.</p></abstract><textClass><keywords scheme="keyword"><list><head>article-category</head><item><term>Research Paper</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1994-04-28">Modified</change><change when="1994">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-ZCTDQXX1-H/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity><istex:entity SYSTEM="gr5" NDATA="IMAGE" name="gr5"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>CURBIO</jid><aid>3</aid><ce:pii>S0960-9822(00)00110-X</ce:pii><ce:doi>10.1016/S0960-9822(00)00110-X</ce:doi><ce:copyright type="full-transfer" year="1994">Elsevier Science Ltd</ce:copyright><ce:doctopics><ce:doctopic><ce:text>Research Paper</ce:text></ce:doctopic></ce:doctopics></item-info><head><ce:dochead><ce:textfn>Research Paper</ce:textfn></ce:dochead><ce:title>Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4<ce:sup>+</ce:sup> T-cell help in CD8<ce:sup>+</ce:sup> T-cell responses</ce:title><ce:author-group><ce:author biographyid="BIO1"><ce:given-name>Yan</ce:given-name><ce:surname>Wu</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>1</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Yang</ce:given-name><ce:surname>Liu</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>1</ce:sup></ce:cross-ref><ce:cross-ref refid="COR1">*</ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>1</ce:label><ce:textfn>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</ce:textfn></ce:affiliation><ce:correspondence id="COR1"><ce:label>*</ce:label><ce:text>Corresponding author.</ce:text></ce:correspondence></ce:author-group><ce:date-received day="28" month="2" year="1994"></ce:date-received><ce:date-revised day="28" month="4" year="1994"></ce:date-revised><ce:date-accepted day="10" month="5" year="1994"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para id="simple-para0030"><ce:bold>Background:</ce:bold> CD4<ce:sup>+</ce:sup> T-cell help is critical for cytotoxic (CD8<ce:sup>+</ce:sup>) T-lymphocyte responses to many antigens, such as viruses, minor histocompatibility antigens and allogeneic major histocompatibility antigens. However, the nature of such help is still a mystery: cytokines such as interleukin-2 may be involved but cell–cell contact may also be necessary. As some viruses can induce CD8<ce:sup>+</ce:sup> T-cell responses in the absence of CD4<ce:sup>+</ce:sup> T cells, we asked whether these viruses and CD4<ce:sup>+</ce:sup> T cells share a pathway for helping the CD8<ce:sup>+</ce:sup> T-cell response.</ce:simple-para><ce:simple-para id="simple-para0035"><ce:bold>Results</ce:bold> We show here that the H2N2 subtype of influenza virus, which elicits a CD4<ce:sup>+</ce:sup> T-cell-independent anti-viral CD8<ce:sup>+</ce:sup> T-cell response <ce:italic>in vitro,</ce:italic> induces expression of the co-stimulatory molecule B7-2, but not of B7, on the cell surface of antigen-presenting cells. In contrast, the H1N1 subtype of influenza virus, which requires CD4<ce:sup>+</ce:sup> T-cell help to elicit CD8<ce:sup>+</ce:sup> T-cell responses under the same conditions, does not induce B7-2 expression. We also find that CD4<ce:sup>+</ce:sup> T cells can induce expression of B7-2 on antigen-presenting cells. In both cases, the induced B7-2 is necessary for the clonal expansion and functional maturation of CD8<ce:sup>+</ce:sup> T cells.</ce:simple-para><ce:simple-para id="simple-para0040"><ce:bold>Conclusion</ce:bold> Our results support the view that the induction of co-stimulatory activity on antigen-presenting cells by CD4<ce:sup>+</ce:sup> T cells can substitute for the requirement for exogenous interleukin-2 in CD8<ce:sup>+</ce:sup> T-cell help. Viruses that can induce co-stimulatory activity on antigen-presenting cells thus induce a CD4<ce:sup>+</ce:sup> T-cell-independent CD8<ce:sup>+</ce:sup> T-cell response. These findings could explain the reported differences in the requirements for CD4<ce:sup>+</ce:sup> T cells in CD8<ce:sup>+</ce:sup> T-cell responses.</ce:simple-para></ce:abstract-sec></ce:abstract></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4+ T-cell help in CD8+ T-cell responses</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4</title></titleInfo><name type="personal"><namePart type="given">Yan</namePart><namePart type="family">Wu</namePart><affiliation>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yang</namePart><namePart type="family">Liu</namePart><affiliation>Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA</affiliation><description>Corresponding author.</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1994</dateIssued><dateModified encoding="w3cdtf">1994-04-28</dateModified><copyrightDate encoding="w3cdtf">1994</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: Background: CD4+ T-cell help is critical for cytotoxic (CD8+) T-lymphocyte responses to many antigens, such as viruses, minor histocompatibility antigens and allogeneic major histocompatibility antigens. However, the nature of such help is still a mystery: cytokines such as interleukin-2 may be involved but cell–cell contact may also be necessary. As some viruses can induce CD8+ T-cell responses in the absence of CD4+ T cells, we asked whether these viruses and CD4+ T cells share a pathway for helping the CD8+ T-cell response.Results We show here that the H2N2 subtype of influenza virus, which elicits a CD4+ T-cell-independent anti-viral CD8+ T-cell response in vitro, induces expression of the co-stimulatory molecule B7-2, but not of B7, on the cell surface of antigen-presenting cells. In contrast, the H1N1 subtype of influenza virus, which requires CD4+ T-cell help to elicit CD8+ T-cell responses under the same conditions, does not induce B7-2 expression. We also find that CD4+ T cells can induce expression of B7-2 on antigen-presenting cells. In both cases, the induced B7-2 is necessary for the clonal expansion and functional maturation of CD8+ T cells.Conclusion Our results support the view that the induction of co-stimulatory activity on antigen-presenting cells by CD4+ T cells can substitute for the requirement for exogenous interleukin-2 in CD8+ T-cell help. Viruses that can induce co-stimulatory activity on antigen-presenting cells thus induce a CD4+ T-cell-independent CD8+ T-cell response. These findings could explain the reported differences in the requirements for CD4+ T cells in CD8+ T-cell responses.</abstract><note type="content">Section title: Research Paper</note><note type="content">Figure 1: Induction of the co-stimulatory molecule B7-2 on non-T spleen cells in BALB/c ByJ mice by influenza virus. The figure shows flow-cytometry analyses of the expression on influenza virus-infected or uninfected non-T spleen cells of the surface molecules B7, B7-2, HSA and, as a control, immunoglobulin Fc receptor (FcR). T-depleted spleen cells from BALB/cByJ mice were stimulated with either H1N1 or H2N2 subtypes of influenza virus for 16 hours. The viable cells (106 per sample) were incubated with saturating amounts of monoclonal antibodies (mAbs) against B7 (3A12) [24], B7-2 (GL-1) [25], HSA (20C9) [20] and FcR (2.4G2) [44]. The binding of 20C9 and 3A12 was detected by FITC-labeled goat anti-hamster IgG, whereas the binding of 2.G2 and GL-1 was detected by FITC-labeled mouse anti-rat IgG.</note><note type="content">Figure 2: Clonal expansion and functional maturation of CD8+ T cells induced by anti-CD3 mAb and virus-infected antigen-presenting cells. (a) Proliferation of CD8+ T cells when non-T spleen cells stimulated by influenza virus strains H1N1 (PR8) or H2N2 (A/JAP) were used as antigen-presenting cells. Viable, virus-infected or uninfected non-T spleen cells were fixed and compared for their co-stimulatory activity for CD8+ T cells (5 x 104 per well), as assayed by the proliferation of CD8+ T cells in response to anti-CD3 mAb. (b) Inhibition of co-stimulatory activity by anti-B7-2 mAb (GL-1) or anti-B7 mAb (3A12). CD8+ T cells (5 x 104 per well) and fixed, A/JAP-infected non-T spleen cells (105 per well) were incubated in the presence of anti-CD3 mAb and varying concentrations of the anti-B7-2 or anti-B7 mAbs. (c) Cytotoxicity of CD8+ T cells activated by anti-CD3 mAb plus antigen-presenting cells. CD8+ T cells (3 x 106) were activated by anti-CD3 plus fixed, virus-stimulated, syngeneic antigen-presenting cells (6 x 106) for 72 hours, and the cytotoxicity determined by an anti-CD3 redirected lysis assay, using P815 cells as targets. When unstimulated or H1N1 virus-stimulated antigen-presenting cells were used, the CD8 T cell yield is 1.2 x 106, whereas when H2N2 virus-activated antigen-presenting cells were used, the CD8+ T cell yield is 6 x 106. Effector T cells are titrated to give different ratios of effector: target cells (E/T).</note><note type="content">Figure 3: Induction of co-stimulatory activity on spleen accessory cells. (a) CD4+ but not CD8+ T cells induce co-stimulatory activity on antigen-presenting cells (APCs). Aliquots of spleen cells received either one of the following treatments: complement alone (C′), anti-CD4 mAb plus complement (CD4–), anti-CD8 mAb plus complement (CD8–) or anti-CD4 plus anti-CD8 plus complement (CD4–CD8–). These preparations of spleen cells were cultured for 16 hours in the presence or absence of anti-CD3 mAb (@CD3). (b) Induction of co-stimulatory activity on antigen-presenting cells requires contact between T cells and antigen-presenting cells. Total spleen cells (upper chambers) and T-depleted cells (lower chambers) were separated by a 0.4 μm polycarbonate membrane. The cell preparations were cultured in the presence or absence of a 1:40 dilution of anti-CD3 for 16 hours and treated with anti-Thy1.2 plus complement to deplete T cells. The T-depleted cells were fixed and used as antigen-presenting cells. The proliferative responses of CD8+ T cells to added anti-CD3 mAb were measured as described in Material and methods. (c) Anti-CD3-redirected cytotoxicity of the activated CD8+ T cells. CD8+ T cells (3 x 106) stimulated by anti-CD3 plus different accessory cells (3 x 106) were incubated with 51Cr-labeled P815 cells for 6 hours, and the CD8+ T-cell activity determined by specific lysis (%). Equal fractions of viable cells recovered are used as effector cells in the two groups. As the cell yields are different, the ratios of effector: target cells (E/T) are different. When antigen-presenting cells are isolated from anti-CD3-stimulated spleen cells, the E/T ratios are 90, 30, 10, 3, 1 and 0.3; whereas when antigen-presenting cells are isolated from unstimulated spleen cells, the E/T ratios are 60, 20, 6.6, 2.2, 0.7, and 0.23.</note><note type="content">Figure 4: B7-2 and HSA, but not B7, contribute to the co-stimulatory activity on antigen-presenting cells induced by anti-CD3 activated T cells. (a) Induction of B7-2, but not B7 or HSA, by anti-CD3 activated T cells, as determined by flow cytometry using biotinylated anti-B7-2 (GL-1) [25], anti-B7 (7A5) [24], or anti-HSA (20C9) [20] mAbs. The binding of these mAbs was detected using phycoerythrin-labeled avidin. Data shown are flow cytometric profiles of T-depleted spleen cells cultured in the presence (continuous lines) or absence (dotted lines) of anti-CD3 mAb. (b) Inhibition of co-stimulatory activity by mAbs. Anti-CD3-activated spleen cells were depleted of T cells and fixed by paraformaldehyde. The fixed antigen-presenting cells and anti-CD3 mAb were used to activate CD8+ T cells purified from syngeneic spleen cells. Purified mAbs specific for B7, B7-2 and HSA were added at the beginning of the culture.</note><note type="content">Figure 5: Viral induction of co-stimulatory activity on antigen-presenting cells bypasses CD4+ T-cell help in CD8+ T-cell responses. (a) The CD4+ T-cell receptor recognizes MHC class II–peptide complexes on antigen-presenting cells; this interaction either directly or indirectly (through a CD40–CD40 ligand interaction, or through cytokine production) induces the expression of co-stimulatory activity (Cos) on antigen-presenting cells. (b) The antigen-presenting cells with the induced co-stimulatory activity can activate CD8+ T cells directly, via a receptor (Cos R) for the co-stimulatory activity. (c) Viral infection can induce co-stimulatory activity on antigen-presenting cells either directly, as shown in this report, or possibly indirectly, by inducing non-specific host responses such as activation of natural killer cells, that in turn produce interferon γ, a potent inducer of B7-2 on antigen-presenting cells. CD8+ T cells can then be activated by antigen-presenting cells in the absence of CD4+ T cells (b).</note><subject><genre>article-category</genre><topic>Research Paper</topic></subject><relatedItem type="host"><titleInfo><title>Current Biology</title></titleInfo><titleInfo type="abbreviated"><title>CURBIO</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1994</dateIssued></originInfo><identifier type="ISSN">0960-9822</identifier><identifier type="PII">S0960-9822(00)X0201-1</identifier><part><date>1994</date><detail type="volume"><number>4</number><caption>vol.</caption></detail><detail type="issue"><number>6</number><caption>no.</caption></detail><extent unit="issue-pages"><start>477</start><end>572</end></extent><extent unit="pages"><start>499</start><end>505</end></extent></part></relatedItem><identifier type="istex">85C4D5CBFBBA979B81FD56C641D24C8A231154B1</identifier><identifier type="ark">ark:/67375/6H6-ZCTDQXX1-H</identifier><identifier type="DOI">10.1016/S0960-9822(00)00110-X</identifier><identifier type="PII">S0960-9822(00)00110-X</identifier><accessCondition type="use and reproduction" contentType="copyright">©1994 Elsevier Science Ltd</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Elsevier Science Ltd, ©1994</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-ZCTDQXX1-H/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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