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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset.</title><author><name sortKey="King, C L" sort="King, C L" uniqKey="King C" first="C L" last="King">C L King</name></author><author><name sortKey="Mahanty, S" sort="Mahanty, S" uniqKey="Mahanty S" first="S" last="Mahanty">S. Mahanty</name></author><author><name sortKey="Kumaraswami, V" sort="Kumaraswami, V" uniqKey="Kumaraswami V" first="V" last="Kumaraswami">V. Kumaraswami</name></author><author><name sortKey="Abrams, J S" sort="Abrams, J S" uniqKey="Abrams J" first="J S" last="Abrams">J S Abrams</name></author><author><name sortKey="Regunathan, J" sort="Regunathan, J" uniqKey="Regunathan J" first="J" last="Regunathan">J. Regunathan</name></author><author><name sortKey="Jayaraman, K" sort="Jayaraman, K" uniqKey="Jayaraman K" first="K" last="Jayaraman">K. Jayaraman</name></author><author><name sortKey="Ottesen, E A" sort="Ottesen, E A" uniqKey="Ottesen E" first="E A" last="Ottesen">E A Ottesen</name></author><author><name sortKey="Nutman, T B" sort="Nutman, T B" uniqKey="Nutman T" first="T B" last="Nutman">T B Nutman</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">8408619</idno><idno type="pmc">288325</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC288325</idno><idno type="RBID">PMC:288325</idno><date when="1993">1993</date><idno type="wicri:Area/Pmc/Corpus">001831</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001831</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset.</title><author><name sortKey="King, C L" sort="King, C L" uniqKey="King C" first="C L" last="King">C L King</name></author><author><name sortKey="Mahanty, S" sort="Mahanty, S" uniqKey="Mahanty S" first="S" last="Mahanty">S. Mahanty</name></author><author><name sortKey="Kumaraswami, V" sort="Kumaraswami, V" uniqKey="Kumaraswami V" first="V" last="Kumaraswami">V. Kumaraswami</name></author><author><name sortKey="Abrams, J S" sort="Abrams, J S" uniqKey="Abrams J" first="J S" last="Abrams">J S Abrams</name></author><author><name sortKey="Regunathan, J" sort="Regunathan, J" uniqKey="Regunathan J" first="J" last="Regunathan">J. Regunathan</name></author><author><name sortKey="Jayaraman, K" sort="Jayaraman, K" uniqKey="Jayaraman K" first="K" last="Jayaraman">K. Jayaraman</name></author><author><name sortKey="Ottesen, E A" sort="Ottesen, E A" uniqKey="Ottesen E" first="E A" last="Ottesen">E A Ottesen</name></author><author><name sortKey="Nutman, T B" sort="Nutman, T B" uniqKey="Nutman T" first="T B" last="Nutman">T B Nutman</name></author></analytic><series><title level="j">Journal of Clinical Investigation</title><idno type="ISSN">0021-9738</idno><imprint><date when="1993">1993</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The immunological mechanisms involved in maintenance of an asymptomatic microfilaremic state (MF) in patients with lymphatic filariasis remain undefined. MF patients have impaired filarial antigen (Ag)-specific lymphocyte proliferation and decreased frequencies (Fo) of Ag-specific T cells, and yet elevated serum IgE and antifilarial IgG4. To investigate the mechanism of Ag-specific anergy in MF patients in contrast to amicrofilaremic individuals with chronic lymphatic obstruction (CP), the Fo of Ag-specific lymphocytes from peripheral blood mononuclear cells secreting either IL-4 or IFN-gamma were assessed by filter spot enzyme-linked immunosorbent assay, and IL-10 and transforming growth factor-beta (TGF-beta) mRNA transcript levels were assessed by a semiquantitative reverse transcriptase polymerase chain reaction technique. The Fo of filaria-specific IL-4-secreting lymphocytes were equivalent in both MF (geometric mean [GM] = 1:11,700) and CP (GM = 1:29,300 P = 0.08), whereas the Fo of IFN-gamma-secreting lymphocytes were lower in MF (GM = 1:39,300) than in CP (GM = 1:4,200, P < 0.01). When the ratio of IL-4/IFN-gamma (T helper type 2 [Th2]/Th1)-secreting cells was examined, MF subjects showed a predominant Th2 response (8:1) compared with a Th1 response in CP individuals (1:4). mRNA transcript levels of IL-10 were also significantly elevated in MF compared with CP individuals (P < 0.01). Further, IL-10 and TGF-beta were shown to have a role in modulating the Ag-specific anergy among MF subjects, in that neutralizing anti-IL-10 or anti-TGF-beta significantly enhanced lymphocyte proliferation response (by 220-1,300%) to filarial Ags in MF individuals. These findings demonstrate that MF subjects respond to parasite antigen by producing a set of suppressive cytokines that may facilitate persistence of the parasite within humans while producing little clinical disease.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Invest</journal-id><journal-title>Journal of Clinical Investigation</journal-title><issn pub-type="ppub">0021-9738</issn></journal-meta><article-meta><article-id pub-id-type="pmid">8408619</article-id><article-id pub-id-type="pmc">288325</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset.</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>King</surname><given-names>C L</given-names></name></contrib><contrib contrib-type="author"><name><surname>Mahanty</surname><given-names>S</given-names></name></contrib><contrib contrib-type="author"><name><surname>Kumaraswami</surname><given-names>V</given-names></name></contrib><contrib contrib-type="author"><name><surname>Abrams</surname><given-names>J S</given-names></name></contrib><contrib contrib-type="author"><name><surname>Regunathan</surname><given-names>J</given-names></name></contrib><contrib contrib-type="author"><name><surname>Jayaraman</surname><given-names>K</given-names></name></contrib><contrib contrib-type="author"><name><surname>Ottesen</surname><given-names>E A</given-names></name></contrib><contrib contrib-type="author"><name><surname>Nutman</surname><given-names>T B</given-names></name></contrib></contrib-group><aff>Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland 20892.</aff><pub-date pub-type="ppub"><month>10</month><year>1993</year></pub-date><volume>92</volume><issue>4</issue><fpage>1667</fpage><lpage>1673</lpage><abstract><p>The immunological mechanisms involved in maintenance of an asymptomatic microfilaremic state (MF) in patients with lymphatic filariasis remain undefined. MF patients have impaired filarial antigen (Ag)-specific lymphocyte proliferation and decreased frequencies (Fo) of Ag-specific T cells, and yet elevated serum IgE and antifilarial IgG4. To investigate the mechanism of Ag-specific anergy in MF patients in contrast to amicrofilaremic individuals with chronic lymphatic obstruction (CP), the Fo of Ag-specific lymphocytes from peripheral blood mononuclear cells secreting either IL-4 or IFN-gamma were assessed by filter spot enzyme-linked immunosorbent assay, and IL-10 and transforming growth factor-beta (TGF-beta) mRNA transcript levels were assessed by a semiquantitative reverse transcriptase polymerase chain reaction technique. The Fo of filaria-specific IL-4-secreting lymphocytes were equivalent in both MF (geometric mean [GM] = 1:11,700) and CP (GM = 1:29,300 P = 0.08), whereas the Fo of IFN-gamma-secreting lymphocytes were lower in MF (GM = 1:39,300) than in CP (GM = 1:4,200, P < 0.01). When the ratio of IL-4/IFN-gamma (T helper type 2 [Th2]/Th1)-secreting cells was examined, MF subjects showed a predominant Th2 response (8:1) compared with a Th1 response in CP individuals (1:4). mRNA transcript levels of IL-10 were also significantly elevated in MF compared with CP individuals (P < 0.01). Further, IL-10 and TGF-beta were shown to have a role in modulating the Ag-specific anergy among MF subjects, in that neutralizing anti-IL-10 or anti-TGF-beta significantly enhanced lymphocyte proliferation response (by 220-1,300%) to filarial Ags in MF individuals. These findings demonstrate that MF subjects respond to parasite antigen by producing a set of suppressive cytokines that may facilitate persistence of the parasite within humans while producing little clinical disease.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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