SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy
Identifieur interne : 001B02 ( Istex/Corpus ); précédent : 001B01; suivant : 001B03SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy
Auteurs : Lucy M. Carruth ; M. Christine Zink ; Patrick M. Tarwater ; Michael D. Miller ; Ming Li ; Laurie A. Queen ; Joseph L. Mankowski ; Anding Shen ; Robert F. Siliciano ; Janice E. ClementsSource :
- Journal of Medical Primatology [ 0047-2565 ] ; 2005-06.
Abstract
Abstract: There is currently no SIV macaque model in which the effects of combination antiretroviral therapy on tissue immune responses and latent reservoirs have been measured. This study was performed to define the impact of combination therapy on the specificity and distribution of the T lymphocyte response in multiple tissue compartments. Pigtailed macaques (Macaca nemestrina) were infected with SIV/17E‐Fr and treated with combination antiretroviral therapy consisting of 9‐R‐(2‐phosphonomethoxypropyl)adenine (PMPA) and beta‐2′,3′‐dideoxy‐3′‐thia‐5‐fluorocytidine (FTC). The SIV‐specific T lymphocyte response was measured in peripheral blood, spleen and several lymph nodes at necropsy by IFN‐γ Elispot analysis. Two animals (one treated, one untreated) had high acute peak viremia, which was associated with lower SIV‐specific T lymphocyte responses in the peripheral blood and lymphoid tissues. In the treated animal, viremia was controlled to low or undetectable for the study duration, and virus‐specific responses remained low. The untreated animal remained viremic throughout the study and developed clinical symptoms of AIDS. In contrast, the two animals that had lower acute peak viremia (one treated, one untreated) had more robust T lymphocyte responses, and controlled viral replication. Virus‐specific responses were detected in the treated animal despite 6 months of suppressive therapy. These data suggest that in this model, in the context of acute peak viremia and weak T cell responses, combination therapy may be essential to control virus replication and disease progression. Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response.
Url:
DOI: 10.1111/j.1600-0684.2005.00103.x
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Carruth</name><affiliation><mods:affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Christine Zink, M" sort="Christine Zink, M" uniqKey="Christine Zink M" first="M." last="Christine Zink">M. Christine Zink</name><affiliation><mods:affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Tarwater, Patrick M" sort="Tarwater, Patrick M" uniqKey="Tarwater P" first="Patrick M." last="Tarwater">Patrick M. Tarwater</name><affiliation><mods:affiliation>Department of Biostatistics, University of Texas School of Public Health Houston, El Paso, TX</mods:affiliation></affiliation></author><author><name sortKey="Miller, Michael D" sort="Miller, Michael D" uniqKey="Miller M" first="Michael D." last="Miller">Michael D. Miller</name><affiliation><mods:affiliation>Clinical Virology, Gilead Sciences, Inc., Foster City, CA</mods:affiliation></affiliation></author><author><name sortKey="Li, Ming" sort="Li, Ming" uniqKey="Li M" first="Ming" last="Li">Ming Li</name><affiliation><mods:affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Queen, Laurie A" sort="Queen, Laurie A" uniqKey="Queen L" first="Laurie A." last="Queen">Laurie A. Queen</name><affiliation><mods:affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Mankowski, Joseph L" sort="Mankowski, Joseph L" uniqKey="Mankowski J" first="Joseph L." last="Mankowski">Joseph L. Mankowski</name><affiliation><mods:affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Shen, Anding" sort="Shen, Anding" uniqKey="Shen A" first="Anding" last="Shen">Anding Shen</name><affiliation><mods:affiliation>Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA</mods:affiliation></affiliation></author><author><name sortKey="Siliciano, Robert F" sort="Siliciano, Robert F" uniqKey="Siliciano R" first="Robert F." last="Siliciano">Robert F. Siliciano</name><affiliation><mods:affiliation>Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA</mods:affiliation></affiliation></author><author><name sortKey="Clements, Janice E" sort="Clements, Janice E" uniqKey="Clements J" first="Janice E." last="Clements">Janice E. Clements</name><affiliation><mods:affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Medical Primatology</title><title level="j" type="alt">JOURNAL OF MEDICAL PRIMATOLOGY</title><idno type="ISSN">0047-2565</idno><idno type="eISSN">1600-0684</idno><imprint><biblScope unit="vol">34</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="109">109</biblScope><biblScope unit="page" to="121">121</biblScope><biblScope unit="page-count">13</biblScope><publisher>Munksgaard International Publishers</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2005-06">2005-06</date></imprint><idno type="ISSN">0047-2565</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0047-2565</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: There is currently no SIV macaque model in which the effects of combination antiretroviral therapy on tissue immune responses and latent reservoirs have been measured. This study was performed to define the impact of combination therapy on the specificity and distribution of the T lymphocyte response in multiple tissue compartments. Pigtailed macaques (Macaca nemestrina) were infected with SIV/17E‐Fr and treated with combination antiretroviral therapy consisting of 9‐R‐(2‐phosphonomethoxypropyl)adenine (PMPA) and beta‐2′,3′‐dideoxy‐3′‐thia‐5‐fluorocytidine (FTC). The SIV‐specific T lymphocyte response was measured in peripheral blood, spleen and several lymph nodes at necropsy by IFN‐γ Elispot analysis. Two animals (one treated, one untreated) had high acute peak viremia, which was associated with lower SIV‐specific T lymphocyte responses in the peripheral blood and lymphoid tissues. In the treated animal, viremia was controlled to low or undetectable for the study duration, and virus‐specific responses remained low. The untreated animal remained viremic throughout the study and developed clinical symptoms of AIDS. In contrast, the two animals that had lower acute peak viremia (one treated, one untreated) had more robust T lymphocyte responses, and controlled viral replication. Virus‐specific responses were detected in the treated animal despite 6 months of suppressive therapy. These data suggest that in this model, in the context of acute peak viremia and weak T cell responses, combination therapy may be essential to control virus replication and disease progression. Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>lymphocyte</json:string><json:string>macaque</json:string><json:string>lymphoid</json:string><json:string>viremia</json:string><json:string>immune</json:string><json:string>elispot</json:string><json:string>viral</json:string><json:string>lymphoid tissue</json:string><json:string>antiretroviral</json:string><json:string>peripheral blood</json:string><json:string>immune response</json:string><json:string>node</json:string><json:string>virol</json:string><json:string>lymphocyte response</json:string><json:string>simian</json:string><json:string>peptide</json:string><json:string>elispot response</json:string><json:string>lymph node</json:string><json:string>cell response</json:string><json:string>pbmc</json:string><json:string>pigtailed</json:string><json:string>untreated</json:string><json:string>cytotoxic</json:string><json:string>untreated animal</json:string><json:string>subset</json:string><json:string>rhesus</json:string><json:string>carruth</json:string><json:string>datum</json:string><json:string>pigtailed macaque</json:string><json:string>active antiretroviral therapy</json:string><json:string>acute infection</json:string><json:string>disease progression</json:string><json:string>replication</json:string><json:string>control virus replication</json:string><json:string>latently</json:string><json:string>becton</json:string><json:string>macaca</json:string><json:string>cell count</json:string><json:string>viral load</json:string><json:string>nemestrina</json:string><json:string>becton dickinson</json:string><json:string>peak viremia</json:string><json:string>lymphocyte count</json:string><json:string>lymphocyte subset</json:string><json:string>assay</json:string><json:string>lymph</json:string><json:string>untreated macaque</json:string><json:string>rhesus monkey</json:string><json:string>human virus type</json:string><json:string>input cell</json:string><json:string>rhesus macaque</json:string><json:string>antiretroviral therapy</json:string><json:string>combination therapy</json:string><json:string>antiretroviral treatment</json:string><json:string>macaca nemestrina</json:string><json:string>treatment interruption</json:string><json:string>individual peptide</json:string><json:string>spleen</json:string><json:string>virus replication</json:string><json:string>plasma viremia</json:string><json:string>high peak viremia</json:string><json:string>lower peak viremia</json:string><json:string>chronic infection</json:string><json:string>infection</json:string><json:string>necropsy</json:string><json:string>dickinson</json:string><json:string>lifson</json:string><json:string>cell ratio</json:string><json:string>viral replication</json:string><json:string>time point</json:string><json:string>peptide pool</json:string><json:string>cellular immune response</json:string><json:string>high acute peak viremia</json:string><json:string>lower viral load</json:string><json:string>gilead science</json:string><json:string>plasma viral load</json:string><json:string>john hopkins university school</json:string><json:string>latent reservoir</json:string><json:string>distinct lymphoid tissue</json:string><json:string>simian virus</json:string><json:string>early infection</json:string><json:string>single pool</json:string><json:string>simian virus infection</json:string></teeft></keywords><author><json:item><name>Lucy M. Carruth</name><affiliations><json:string>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>M. Christine Zink</name><affiliations><json:string>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Patrick M. Tarwater</name><affiliations><json:string>Department of Biostatistics, University of Texas School of Public Health Houston, El Paso, TX</json:string></affiliations></json:item><json:item><name>Michael D. Miller</name><affiliations><json:string>Clinical Virology, Gilead Sciences, Inc., Foster City, CA</json:string></affiliations></json:item><json:item><name>Ming Li</name><affiliations><json:string>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Laurie A. Queen</name><affiliations><json:string>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Joseph L. Mankowski</name><affiliations><json:string>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Anding Shen</name><affiliations><json:string>Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA</json:string></affiliations></json:item><json:item><name>Robert F. Siliciano</name><affiliations><json:string>Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA</json:string></affiliations></json:item><json:item><name>Janice E. Clements</name><affiliations><json:string>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>cytotoxic T lymphocyte</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Elispot</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>highly active antiretroviral therapy</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>lymph node</value></json:item></subject><articleId><json:string>JMP103</json:string></articleId><arkIstex>ark:/67375/WNG-9PFDZ1DW-7</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Abstract: There is currently no SIV macaque model in which the effects of combination antiretroviral therapy on tissue immune responses and latent reservoirs have been measured. This study was performed to define the impact of combination therapy on the specificity and distribution of the T lymphocyte response in multiple tissue compartments. Pigtailed macaques (Macaca nemestrina) were infected with SIV/17E‐Fr and treated with combination antiretroviral therapy consisting of 9‐R‐(2‐phosphonomethoxypropyl)adenine (PMPA) and beta‐2′,3′‐dideoxy‐3′‐thia‐5‐fluorocytidine (FTC). The SIV‐specific T lymphocyte response was measured in peripheral blood, spleen and several lymph nodes at necropsy by IFN‐γ Elispot analysis. Two animals (one treated, one untreated) had high acute peak viremia, which was associated with lower SIV‐specific T lymphocyte responses in the peripheral blood and lymphoid tissues. In the treated animal, viremia was controlled to low or undetectable for the study duration, and virus‐specific responses remained low. The untreated animal remained viremic throughout the study and developed clinical symptoms of AIDS. In contrast, the two animals that had lower acute peak viremia (one treated, one untreated) had more robust T lymphocyte responses, and controlled viral replication. Virus‐specific responses were detected in the treated animal despite 6 months of suppressive therapy. These data suggest that in this model, in the context of acute peak viremia and weak T cell responses, combination therapy may be essential to control virus replication and disease progression. Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response.</abstract><qualityIndicators><score>9.964</score><pdfWordCount>7421</pdfWordCount><pdfCharCount>48696</pdfCharCount><pdfVersion>1.4</pdfVersion><pdfPageCount>13</pdfPageCount><pdfPageSize>595 x 782 pts</pdfPageSize><pdfWordsPerPage>571</pdfWordsPerPage><pdfText>true</pdfText><refBibsNative>true</refBibsNative><abstractWordCount>247</abstractWordCount><abstractCharCount>1759</abstractCharCount><keywordCount>4</keywordCount></qualityIndicators><title>SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy</title><pmid><json:string>15860119</json:string></pmid><genre><json:string>article</json:string></genre><host><title>Journal of Medical Primatology</title><language><json:string>unknown</json:string></language><doi><json:string>10.1111/(ISSN)1600-0684</json:string></doi><issn><json:string>0047-2565</json:string></issn><eissn><json:string>1600-0684</json:string></eissn><publisherId><json:string>JMP</json:string></publisherId><volume>34</volume><issue>3</issue><pages><first>109</first><last>121</last><total>13</total></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2005</json:string></date><geogName></geogName><orgName><json:string>Gilead Sciences, Inc.</json:string><json:string>Triangle Pharmaceuticals, Inc., Durham</json:string><json:string>Bioqual Inc.</json:string><json:string>Johns Hopkins University</json:string><json:string>Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA Key</json:string><json:string>American Veterinary Medical Association</json:string><json:string>Department of Biostatistics, University of Texas School of Public Health Houston, El Paso, TX</json:string><json:string>Division of Comparative Medicine</json:string><json:string>Mabtech</json:string><json:string>AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Robert F. 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16, 20, 24, 38, 39, 43]</json:string><json:string>[52]</json:string><json:string>[2, 11]</json:string><json:string>Carruth et al.</json:string><json:string>[6, 21, 26, 27, 40]</json:string><json:string>Altfeld et al.</json:string><json:string>[2]</json:string><json:string>[13, 33, 55]</json:string><json:string>[15, 45, 50, 56]</json:string><json:string>[22, 34, 37, 51, 54, 55]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/WNG-9PFDZ1DW-7</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - zoology</json:string><json:string>2 - veterinary sciences</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - virology</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Veterinary</json:string><json:string>3 - General Veterinary</json:string><json:string>1 - Life 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responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy</title><title level="a" type="short">T cell responses in treated SIV‐infected macaques</title><author xml:id="author-0000"><persName><forename type="first">Lucy M.</forename><surname>Carruth</surname></persName><affiliation><orgName type="division">Department of Comparative Medicine</orgName><orgName type="institution">Johns Hopkins University School of Medicine</orgName><address><addrLine>Baltimore</addrLine><addrLine>MD</addrLine></address></affiliation></author><author xml:id="author-0001"><persName><forename type="first">M.</forename><surname>Christine Zink</surname></persName><affiliation><orgName type="division">Department of Comparative Medicine</orgName><orgName type="institution">Johns Hopkins University School of Medicine</orgName><address><addrLine>Baltimore</addrLine><addrLine>MD</addrLine></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">Patrick M.</forename><surname>Tarwater</surname></persName><affiliation><orgName type="division">Department of Biostatistics</orgName><orgName type="institution">University of Texas School of Public Health Houston</orgName><address><addrLine>El Paso</addrLine><addrLine>TX</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0003"><persName><forename type="first">Michael D.</forename><surname>Miller</surname></persName><affiliation><orgName type="department">Clinical Virology</orgName><address><addrLine>Gilead Sciences</addrLine><addrLine>Inc., Foster City, CA</addrLine></address></affiliation></author><author xml:id="author-0004"><persName><forename type="first">Ming</forename><surname>Li</surname></persName><affiliation><orgName type="division">Department of Comparative Medicine</orgName><orgName type="institution">Johns Hopkins University School of Medicine</orgName><address><addrLine>Baltimore</addrLine><addrLine>MD</addrLine></address></affiliation></author><author xml:id="author-0005"><persName><forename type="first">Laurie A.</forename><surname>Queen</surname></persName><affiliation><orgName type="division">Department of Comparative Medicine</orgName><orgName type="institution">Johns Hopkins University School of Medicine</orgName><address><addrLine>Baltimore</addrLine><addrLine>MD</addrLine></address></affiliation></author><author xml:id="author-0006"><persName><forename type="first">Joseph L.</forename><surname>Mankowski</surname></persName><affiliation><orgName type="division">Department of Comparative Medicine</orgName><orgName type="institution">Johns Hopkins University School of Medicine</orgName><address><addrLine>Baltimore</addrLine><addrLine>MD</addrLine></address></affiliation></author><author xml:id="author-0007"><persName><forename type="first">Anding</forename><surname>Shen</surname></persName><affiliation><orgName type="division">Department of Medicine</orgName><orgName type="institution">Johns Hopkins University School of Medicine</orgName><address><addrLine>Baltimore</addrLine><addrLine>MD, USA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0008"><persName><forename type="first">Robert F.</forename><surname>Siliciano</surname></persName><affiliation><orgName type="division">Department of Medicine</orgName><orgName type="institution">Johns Hopkins University School of Medicine</orgName><address><addrLine>Baltimore</addrLine><addrLine>MD, USA</addrLine><country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0009"><persName><forename type="first">Janice E.</forename><surname>Clements</surname></persName><affiliation><orgName type="division">Department of Comparative Medicine</orgName><orgName type="institution">Johns Hopkins University School of Medicine</orgName><address><addrLine>Baltimore</addrLine><addrLine>MD</addrLine></address></affiliation></author><idno type="istex">C2C706F73F2A751472881C1A41887546072267F7</idno><idno type="ark">ark:/67375/WNG-9PFDZ1DW-7</idno><idno type="DOI">10.1111/j.1600-0684.2005.00103.x</idno><idno type="unit">JMP103</idno><idno type="toTypesetVersion">file:JMP.JMP103.pdf</idno></analytic><monogr><title level="j" type="main">Journal of Medical Primatology</title><title level="j" type="alt">JOURNAL OF MEDICAL PRIMATOLOGY</title><idno type="pISSN">0047-2565</idno><idno type="eISSN">1600-0684</idno><idno type="book-DOI">10.1111/(ISSN)1600-0684</idno><idno type="book-part-DOI">10.1111/jmp.2005.34.issue-3</idno><idno type="product">JMP</idno><idno type="publisherDivision">ST</idno><imprint><biblScope unit="vol">34</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="109">109</biblScope><biblScope unit="page" to="121">121</biblScope><biblScope unit="page-count">13</biblScope><publisher>Munksgaard International Publishers</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2005-06"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><encodingDesc><schemaRef type="ODD" url="https://xml-schema.delivery.istex.fr/tei-istex.odd"></schemaRef><appInfo><application ident="pub2tei" version="1.0.10" when="2019-12-20"><label>pub2TEI-ISTEX</label><desc>A set of style sheets for converting XML documents encoded in various scientific publisher formats into a common TEI format.
<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract xml:lang="en" style="main"><p><hi rend="bold">Abstract: </hi> There is currently no SIV macaque model in which the effects of combination antiretroviral therapy on tissue immune responses and latent reservoirs have been measured. This study was performed to define the impact of combination therapy on the specificity and distribution of the T lymphocyte response in multiple tissue compartments. Pigtailed macaques (<hi rend="italic">Macaca nemestrina</hi>) were infected with SIV/17E‐Fr and treated with combination antiretroviral therapy consisting of 9‐R‐(2‐phosphonomethoxypropyl)adenine (PMPA) and beta‐2′,3′‐dideoxy‐3′‐thia‐5‐fluorocytidine (FTC). The SIV‐specific T lymphocyte response was measured in peripheral blood, spleen and several lymph nodes at necropsy by IFN‐<hi rend="italic">γ</hi> Elispot analysis. Two animals (one treated, one untreated) had high acute peak viremia, which was associated with lower SIV‐specific T lymphocyte responses in the peripheral blood and lymphoid tissues. In the treated animal, viremia was controlled to low or undetectable for the study duration, and virus‐specific responses remained low. The untreated animal remained viremic throughout the study and developed clinical symptoms of AIDS. In contrast, the two animals that had lower acute peak viremia (one treated, one untreated) had more robust T lymphocyte responses, and controlled viral replication. Virus‐specific responses were detected in the treated animal despite 6 months of suppressive therapy. These data suggest that in this model, in the context of acute peak viremia and weak T cell responses, combination therapy may be essential to control virus replication and disease progression. Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response.</p></abstract><textClass><keywords xml:lang="en"><term xml:id="k1">cytotoxic T lymphocyte</term><term xml:id="k2">Elispot</term><term xml:id="k3">highly active antiretroviral therapy</term><term xml:id="k4">lymph node</term></keywords><keywords rend="tocHeading1"><term>Original Articles</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-20" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-9PFDZ1DW-7/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Munksgaard International Publishers</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1600-0684</doi><issn type="print">0047-2565</issn><issn type="electronic">1600-0684</issn><idGroup><id type="product" value="JMP"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="JOURNAL OF MEDICAL PRIMATOLOGY">Journal of Medical Primatology</title></titleGroup></publicationMeta><publicationMeta level="part" position="06003"><doi origin="wiley">10.1111/jmp.2005.34.issue-3</doi><numberingGroup><numbering type="journalVolume" number="34">34</numbering><numbering type="journalIssue" number="3">3</numbering></numberingGroup><coverDate startDate="2005-06">June 2005</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="1" status="forIssue"><doi origin="wiley">10.1111/j.1600-0684.2005.00103.x</doi><idGroup><id type="unit" value="JMP103"></id></idGroup><countGroup><count type="pageTotal" number="13"></count></countGroup><titleGroup><title type="tocHeading1">Original Articles</title></titleGroup><eventGroup><event type="firstOnline" date="2005-04-27"></event><event type="publishedOnlineFinalForm" date="2005-04-27"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.2 mode:FullText source:FullText result:FullText" date="2010-03-11"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-31"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-30"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="109">109</numbering><numbering type="pageLast" number="121">121</numbering></numberingGroup><correspondenceTo>Lucy M. Carruth, PhD, Division of Comparative Medicine, Johns Hopkins University School of Medicine, Jefferson Street Building Room 3‐127, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
Tel.: +410 955 9770; fax: +410 955 9823; e‐mail: <email>lcarruth@jhmi.edu</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:JMP.JMP103.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Accepted October 13, 2004.</unparsedEditorialHistory><countGroup><count type="figureTotal" number="4"></count><count type="tableTotal" number="0"></count></countGroup><titleGroup><title type="main">SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy</title><title type="shortAuthors"><b>Carruth et al.</b></title><title type="short"><b>T cell responses in treated SIV‐infected macaques</b></title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>Lucy M.</givenNames><familyName>Carruth</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>M.</givenNames><familyName>Christine Zink</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a2"><personName><givenNames>Patrick M.</givenNames><familyName>Tarwater</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a3"><personName><givenNames>Michael D.</givenNames><familyName>Miller</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a1"><personName><givenNames>Ming</givenNames><familyName>Li</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a1"><personName><givenNames>Laurie A.</givenNames><familyName>Queen</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a1"><personName><givenNames>Joseph L.</givenNames><familyName>Mankowski</familyName></personName></creator><creator creatorRole="author" xml:id="cr8" affiliationRef="#a4"><personName><givenNames>Anding</givenNames><familyName>Shen</familyName></personName></creator><creator creatorRole="author" xml:id="cr9" affiliationRef="#a4"><personName><givenNames>Robert F.</givenNames><familyName>Siliciano</familyName></personName></creator><creator creatorRole="author" xml:id="cr10" affiliationRef="#a1"><personName><givenNames>Janice E.</givenNames><familyName>Clements</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1"><unparsedAffiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="US"><unparsedAffiliation>Department of Biostatistics, University of Texas School of Public Health Houston, El Paso, TX</unparsedAffiliation></affiliation><affiliation xml:id="a3"><unparsedAffiliation>Clinical Virology, Gilead Sciences, Inc., Foster City, CA</unparsedAffiliation></affiliation><affiliation xml:id="a4" countryCode="US"><unparsedAffiliation>Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">cytotoxic T lymphocyte</keyword><keyword xml:id="k2">Elispot</keyword><keyword xml:id="k3">highly active antiretroviral therapy</keyword><keyword xml:id="k4">lymph node</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p><b>Abstract: </b> There is currently no SIV macaque model in which the effects of combination antiretroviral therapy on tissue immune responses and latent reservoirs have been measured. This study was performed to define the impact of combination therapy on the specificity and distribution of the T lymphocyte response in multiple tissue compartments. Pigtailed macaques (<i>Macaca nemestrina</i>) were infected with SIV/17E‐Fr and treated with combination antiretroviral therapy consisting of 9‐R‐(2‐phosphonomethoxypropyl)adenine (PMPA) and beta‐2′,3′‐dideoxy‐3′‐thia‐5‐fluorocytidine (FTC). The SIV‐specific T lymphocyte response was measured in peripheral blood, spleen and several lymph nodes at necropsy by IFN‐<i>γ</i> Elispot analysis. Two animals (one treated, one untreated) had high acute peak viremia, which was associated with lower SIV‐specific T lymphocyte responses in the peripheral blood and lymphoid tissues. In the treated animal, viremia was controlled to low or undetectable for the study duration, and virus‐specific responses remained low. The untreated animal remained viremic throughout the study and developed clinical symptoms of AIDS. In contrast, the two animals that had lower acute peak viremia (one treated, one untreated) had more robust T lymphocyte responses, and controlled viral replication. Virus‐specific responses were detected in the treated animal despite 6 months of suppressive therapy. These data suggest that in this model, in the context of acute peak viremia and weak T cell responses, combination therapy may be essential to control virus replication and disease progression. Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1" numbered="no"><p>Funding: This study was funded by NIH grants to R.F.S., M.C.Z., and J.E.C. (MH070306‐01AI43222, MH61189, NS35751, NS38008, and NS36911).</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>T cell responses in treated SIV‐infected macaques</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>SIV‐specific T lymphocyte responses in PBMC and lymphoid tissues of SIV‐infected pigtailed macaques during suppressive combination antiretroviral therapy</title></titleInfo><name type="personal"><namePart type="given">Lucy M.</namePart><namePart type="family">Carruth</namePart><affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.</namePart><namePart type="family">Christine Zink</namePart><affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patrick M.</namePart><namePart type="family">Tarwater</namePart><affiliation>Department of Biostatistics, University of Texas School of Public Health Houston, El Paso, TX</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael D.</namePart><namePart type="family">Miller</namePart><affiliation>Clinical Virology, Gilead Sciences, Inc., Foster City, CA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ming</namePart><namePart type="family">Li</namePart><affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Laurie A.</namePart><namePart type="family">Queen</namePart><affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joseph L.</namePart><namePart type="family">Mankowski</namePart><affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anding</namePart><namePart type="family">Shen</namePart><affiliation>Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Robert F.</namePart><namePart type="family">Siliciano</namePart><affiliation>Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Janice E.</namePart><namePart type="family">Clements</namePart><affiliation>Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Munksgaard International Publishers</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2005-06</dateIssued><edition>Accepted October 13, 2004.</edition><copyrightDate encoding="w3cdtf">2005</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">4</extent><extent unit="tables">0</extent></physicalDescription><abstract lang="en">Abstract: There is currently no SIV macaque model in which the effects of combination antiretroviral therapy on tissue immune responses and latent reservoirs have been measured. This study was performed to define the impact of combination therapy on the specificity and distribution of the T lymphocyte response in multiple tissue compartments. Pigtailed macaques (Macaca nemestrina) were infected with SIV/17E‐Fr and treated with combination antiretroviral therapy consisting of 9‐R‐(2‐phosphonomethoxypropyl)adenine (PMPA) and beta‐2′,3′‐dideoxy‐3′‐thia‐5‐fluorocytidine (FTC). The SIV‐specific T lymphocyte response was measured in peripheral blood, spleen and several lymph nodes at necropsy by IFN‐γ Elispot analysis. Two animals (one treated, one untreated) had high acute peak viremia, which was associated with lower SIV‐specific T lymphocyte responses in the peripheral blood and lymphoid tissues. In the treated animal, viremia was controlled to low or undetectable for the study duration, and virus‐specific responses remained low. The untreated animal remained viremic throughout the study and developed clinical symptoms of AIDS. In contrast, the two animals that had lower acute peak viremia (one treated, one untreated) had more robust T lymphocyte responses, and controlled viral replication. Virus‐specific responses were detected in the treated animal despite 6 months of suppressive therapy. These data suggest that in this model, in the context of acute peak viremia and weak T cell responses, combination therapy may be essential to control virus replication and disease progression. Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response.</abstract><subject lang="en"><genre>keywords</genre><topic>cytotoxic T lymphocyte</topic><topic>Elispot</topic><topic>highly active antiretroviral therapy</topic><topic>lymph node</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Medical Primatology</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><identifier type="ISSN">0047-2565</identifier><identifier type="eISSN">1600-0684</identifier><identifier type="DOI">10.1111/(ISSN)1600-0684</identifier><identifier type="PublisherID">JMP</identifier><part><date>2005</date><detail type="volume"><caption>vol.</caption><number>34</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>109</start><end>121</end><total>13</total></extent></part></relatedItem><relatedItem type="references" displayLabel="cit2"><titleInfo><title>Structured interruptions of therapy: looking for the best protocol</title></titleInfo><name type="personal"><namePart type="given">F</namePart><namePart type="family">Aiuti</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Giovannetti</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Aiuti F, Giovannetti A: Structured interruptions of therapy: looking for the best protocol. 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