Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.
Identifieur interne : 001820 ( Pmc/Corpus ); précédent : 001819; suivant : 001821Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.
Auteurs : C L King ; V. Kumaraswami ; R W Poindexter ; S. Kumari ; K. Jayaraman ; D W Alling ; E A Ottesen ; T B NutmanSource :
- Journal of Clinical Investigation [ 0021-9738 ] ; 1992.
Abstract
To explore the mechanisms of antigen-specific immune unresponsiveness seen in microfilaremic patients with bancroftian filariasis, T and B cell precursor frequency analysis was performed using PBMC from individuals with either asymptomatic microfilaremia (MF, n = 7) or chronic lymphatic obstruction (CP, n = 20). Highly purified CD3+ cells were partially reconstituted with adherent cells and their proliferative response to parasite antigens determined in cultures of T cells by limiting dilution analysis. A filter immunoplaque assay also assessed the frequency of both total and parasite-specific Ig-producing B cells. While the lymphocyte proliferation to mitogens and to a nonparasite antigen (Streptolysin-O, [SLO]) were similar in all groups of patients, the frequency of parasite-specific CD3+ T cells was significantly lower (geometric mean [GM], 1/3,757) in MF patients when compared to that in CP patients (GM 1/1,513; P less than 0.001). Similarly, the proportion of lymphocytes producing parasite-specific IgE or IgG was significantly lower in MF patients (IgE mean, 0.2%; IgG mean, 0.33%) compared with CP patients (IgE mean, 3.2%; IgG mean, 1.76%; P less than 0.05 for both comparisons). These observations imply that low numbers of parasite-specific T and B lymphocytes may be partially responsible for the severely diminished capacity of lymphocytes from patients with MF to produce parasite-specific antibody and to proliferate to parasite antigen in vitro. Such differences in parasite-specific lymphocyte responses suggest that tolerance by clonal anergy may be a critical mechanism for maintaining the microfilaremic state.
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PubMed: 1569183
PubMed Central: 443009
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PMC:443009Le document en format XML
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<author><name sortKey="King, C L" sort="King, C L" uniqKey="King C" first="C L" last="King">C L King</name>
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<author><name sortKey="Kumaraswami, V" sort="Kumaraswami, V" uniqKey="Kumaraswami V" first="V" last="Kumaraswami">V. Kumaraswami</name>
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<author><name sortKey="Poindexter, R W" sort="Poindexter, R W" uniqKey="Poindexter R" first="R W" last="Poindexter">R W Poindexter</name>
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<author><name sortKey="Kumari, S" sort="Kumari, S" uniqKey="Kumari S" first="S" last="Kumari">S. Kumari</name>
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<author><name sortKey="Jayaraman, K" sort="Jayaraman, K" uniqKey="Jayaraman K" first="K" last="Jayaraman">K. Jayaraman</name>
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<author><name sortKey="Alling, D W" sort="Alling, D W" uniqKey="Alling D" first="D W" last="Alling">D W Alling</name>
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<author><name sortKey="Ottesen, E A" sort="Ottesen, E A" uniqKey="Ottesen E" first="E A" last="Ottesen">E A Ottesen</name>
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<author><name sortKey="Nutman, T B" sort="Nutman, T B" uniqKey="Nutman T" first="T B" last="Nutman">T B Nutman</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.</title>
<author><name sortKey="King, C L" sort="King, C L" uniqKey="King C" first="C L" last="King">C L King</name>
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<author><name sortKey="Kumaraswami, V" sort="Kumaraswami, V" uniqKey="Kumaraswami V" first="V" last="Kumaraswami">V. Kumaraswami</name>
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<author><name sortKey="Poindexter, R W" sort="Poindexter, R W" uniqKey="Poindexter R" first="R W" last="Poindexter">R W Poindexter</name>
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<author><name sortKey="Kumari, S" sort="Kumari, S" uniqKey="Kumari S" first="S" last="Kumari">S. Kumari</name>
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<author><name sortKey="Jayaraman, K" sort="Jayaraman, K" uniqKey="Jayaraman K" first="K" last="Jayaraman">K. Jayaraman</name>
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<author><name sortKey="Alling, D W" sort="Alling, D W" uniqKey="Alling D" first="D W" last="Alling">D W Alling</name>
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<series><title level="j">Journal of Clinical Investigation</title>
<idno type="ISSN">0021-9738</idno>
<imprint><date when="1992">1992</date>
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<front><div type="abstract" xml:lang="en"><p>To explore the mechanisms of antigen-specific immune unresponsiveness seen in microfilaremic patients with bancroftian filariasis, T and B cell precursor frequency analysis was performed using PBMC from individuals with either asymptomatic microfilaremia (MF, n = 7) or chronic lymphatic obstruction (CP, n = 20). Highly purified CD3+ cells were partially reconstituted with adherent cells and their proliferative response to parasite antigens determined in cultures of T cells by limiting dilution analysis. A filter immunoplaque assay also assessed the frequency of both total and parasite-specific Ig-producing B cells. While the lymphocyte proliferation to mitogens and to a nonparasite antigen (Streptolysin-O, [SLO]) were similar in all groups of patients, the frequency of parasite-specific CD3+ T cells was significantly lower (geometric mean [GM], 1/3,757) in MF patients when compared to that in CP patients (GM 1/1,513; P less than 0.001). Similarly, the proportion of lymphocytes producing parasite-specific IgE or IgG was significantly lower in MF patients (IgE mean, 0.2%; IgG mean, 0.33%) compared with CP patients (IgE mean, 3.2%; IgG mean, 1.76%; P less than 0.05 for both comparisons). These observations imply that low numbers of parasite-specific T and B lymphocytes may be partially responsible for the severely diminished capacity of lymphocytes from patients with MF to produce parasite-specific antibody and to proliferate to parasite antigen in vitro. Such differences in parasite-specific lymphocyte responses suggest that tolerance by clonal anergy may be a critical mechanism for maintaining the microfilaremic state.</p>
</div>
</front>
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<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">1569183</article-id>
<article-id pub-id-type="pmc">443009</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
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<title-group><article-title>Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.</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>Kumaraswami</surname>
<given-names>V</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Poindexter</surname>
<given-names>R W</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Kumari</surname>
<given-names>S</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>Alling</surname>
<given-names>D W</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>5</month>
<year>1992</year>
</pub-date>
<volume>89</volume>
<issue>5</issue>
<fpage>1403</fpage>
<lpage>1410</lpage>
<abstract><p>To explore the mechanisms of antigen-specific immune unresponsiveness seen in microfilaremic patients with bancroftian filariasis, T and B cell precursor frequency analysis was performed using PBMC from individuals with either asymptomatic microfilaremia (MF, n = 7) or chronic lymphatic obstruction (CP, n = 20). Highly purified CD3+ cells were partially reconstituted with adherent cells and their proliferative response to parasite antigens determined in cultures of T cells by limiting dilution analysis. A filter immunoplaque assay also assessed the frequency of both total and parasite-specific Ig-producing B cells. While the lymphocyte proliferation to mitogens and to a nonparasite antigen (Streptolysin-O, [SLO]) were similar in all groups of patients, the frequency of parasite-specific CD3+ T cells was significantly lower (geometric mean [GM], 1/3,757) in MF patients when compared to that in CP patients (GM 1/1,513; P less than 0.001). Similarly, the proportion of lymphocytes producing parasite-specific IgE or IgG was significantly lower in MF patients (IgE mean, 0.2%; IgG mean, 0.33%) compared with CP patients (IgE mean, 3.2%; IgG mean, 1.76%; P less than 0.05 for both comparisons). These observations imply that low numbers of parasite-specific T and B lymphocytes may be partially responsible for the severely diminished capacity of lymphocytes from patients with MF to produce parasite-specific antibody and to proliferate to parasite antigen in vitro. Such differences in parasite-specific lymphocyte responses suggest that tolerance by clonal anergy may be a critical mechanism for maintaining the microfilaremic state.</p>
</abstract>
</article-meta>
</front>
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</record>
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