Expansion of Parasite-Specific CD4+ and CD8+ T Cells Expressing IL-10 Superfamily Cytokine Members and Their Regulation in Human Lymphatic Filariasis
Identifieur interne : 001B71 ( Pmc/Checkpoint ); précédent : 001B70; suivant : 001B72Expansion of Parasite-Specific CD4+ and CD8+ T Cells Expressing IL-10 Superfamily Cytokine Members and Their Regulation in Human Lymphatic Filariasis
Auteurs : Rajamanickam Anuradha [Inde] ; Parakkal Jovvian George [Inde] ; Luke E. Hanna [Inde] ; Paul Kumaran [Inde] ; Vedachalam Chandrasekaran [Inde] ; Thomas B. Nutman [États-Unis] ; Subash Babu [Inde, États-Unis]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2014.
Abstract
Lymphatic filariasis (LF) is known to be associated with an increased production of IL-10. The role of the other IL-10 family members in the pathogenesis of infection and/or disease is not known.
We examined the expression patterns of IL-10 family members – IL-19, IL-24 and IL-26 in LF. We demonstrate that both CD4+ and CD8+ T cells express IL-19, IL-24 and IL-26 and that the frequency of CD4+ T cells expressing IL-19 and IL-24 (as well as IL-10) is significantly increased at baseline and following filarial antigen stimulation in patients with LF in comparison to individuals with filarial lymphedema and uninfected individuals. This CD4+ T cell expression pattern was associated with increased production of IL-19 and IL-24 by filarial – antigen stimulated PBMC. Moreover, the frequency of CD4+ and CD8+ T cells expressing IL-26 was significantly increased following filarial antigen stimulation in filarial lymphedema individuals. Interestingly, IL-10 blockade resulted in diminished frequencies of IL-19+ and IL-24+ T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of IL-19+ and IL-24+ T cells as well as significantly up regulated IL-19 and IL-24 gene expression, suggesting that IL-10 regulates IL-19 and IL-24 expression in T cells. In addition, IL-1β and IL-23 blockade also induced a diminution in the frequency of IL-19+ and IL-24+ T cells, indicating a novel role for these cytokines in the induction of IL-19 and IL-24 expressing T cells. Finally, elimination of infection resulted in significantly decreased frequencies of antigen – specific CD4+ T cells expressing IL-10, IL-19 and IL-24.
Our findings, therefore, suggest that IL-19 and IL-24 are associated with the regulation of immune responses in active filarial infection and potentially with protection against development of pathology, while IL-26 is predominantly associated with pathology in LF.
Url:
DOI: 10.1371/journal.pntd.0002762
PubMed: 24699268
PubMed Central: 3974669
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Expansion of Parasite-Specific CD4<sup>+</sup> and CD8<sup>+</sup> T Cells Expressing IL-10 Superfamily Cytokine Members and Their Regulation in Human Lymphatic Filariasis</title><author><name sortKey="Anuradha, Rajamanickam" sort="Anuradha, Rajamanickam" uniqKey="Anuradha R" first="Rajamanickam" last="Anuradha">Rajamanickam Anuradha</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health—International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health—International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="George, Parakkal Jovvian" sort="George, Parakkal Jovvian" uniqKey="George P" first="Parakkal Jovvian" last="George">Parakkal Jovvian George</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health—International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health—International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Hanna, Luke E" sort="Hanna, Luke E" uniqKey="Hanna L" first="Luke E." last="Hanna">Luke E. Hanna</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>National Institute for Research in Tuberculosis, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institute for Research in Tuberculosis, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Kumaran, Paul" sort="Kumaran, Paul" uniqKey="Kumaran P" first="Paul" last="Kumaran">Paul Kumaran</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>National Institute for Research in Tuberculosis, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institute for Research in Tuberculosis, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Chandrasekaran, Vedachalam" sort="Chandrasekaran, Vedachalam" uniqKey="Chandrasekaran V" first="Vedachalam" last="Chandrasekaran">Vedachalam Chandrasekaran</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>National Institute for Research in Tuberculosis, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institute for Research in Tuberculosis, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health—International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health—International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24699268</idno><idno type="pmc">3974669</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974669</idno><idno type="RBID">PMC:3974669</idno><idno type="doi">10.1371/journal.pntd.0002762</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">004355</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004355</idno><idno type="wicri:Area/Pmc/Curation">004354</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">004354</idno><idno type="wicri:Area/Pmc/Checkpoint">001B71</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001B71</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Expansion of Parasite-Specific CD4<sup>+</sup> and CD8<sup>+</sup> T Cells Expressing IL-10 Superfamily Cytokine Members and Their Regulation in Human Lymphatic Filariasis</title><author><name sortKey="Anuradha, Rajamanickam" sort="Anuradha, Rajamanickam" uniqKey="Anuradha R" first="Rajamanickam" last="Anuradha">Rajamanickam Anuradha</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health—International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health—International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="George, Parakkal Jovvian" sort="George, Parakkal Jovvian" uniqKey="George P" first="Parakkal Jovvian" last="George">Parakkal Jovvian George</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health—International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health—International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Hanna, Luke E" sort="Hanna, Luke E" uniqKey="Hanna L" first="Luke E." last="Hanna">Luke E. Hanna</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>National Institute for Research in Tuberculosis, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institute for Research in Tuberculosis, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Kumaran, Paul" sort="Kumaran, Paul" uniqKey="Kumaran P" first="Paul" last="Kumaran">Paul Kumaran</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>National Institute for Research in Tuberculosis, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institute for Research in Tuberculosis, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Chandrasekaran, Vedachalam" sort="Chandrasekaran, Vedachalam" uniqKey="Chandrasekaran V" first="Vedachalam" last="Chandrasekaran">Vedachalam Chandrasekaran</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>National Institute for Research in Tuberculosis, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institute for Research in Tuberculosis, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health—International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health—International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j">PLoS Neglected Tropical Diseases</title><idno type="ISSN">1935-2727</idno><idno type="eISSN">1935-2735</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Lymphatic filariasis (LF) is known to be associated with an increased production of IL-10. The role of the other IL-10 family members in the pathogenesis of infection and/or disease is not known.</p></sec><sec><title>Methodology/Principal Findings</title><p>We examined the expression patterns of IL-10 family members – IL-19, IL-24 and IL-26 in LF. We demonstrate that both CD4<sup>+</sup> and CD8<sup>+</sup> T cells express IL-19, IL-24 and IL-26 and that the frequency of CD4<sup>+</sup> T cells expressing IL-19 and IL-24 (as well as IL-10) is significantly increased at baseline and following filarial antigen stimulation in patients with LF in comparison to individuals with filarial lymphedema and uninfected individuals. This CD4<sup>+</sup> T cell expression pattern was associated with increased production of IL-19 and IL-24 by filarial – antigen stimulated PBMC. Moreover, the frequency of CD4<sup>+</sup> and CD8<sup>+</sup> T cells expressing IL-26 was significantly increased following filarial antigen stimulation in filarial lymphedema individuals. Interestingly, IL-10 blockade resulted in diminished frequencies of IL-19<sup>+</sup> and IL-24<sup>+</sup> T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of IL-19<sup>+</sup> and IL-24<sup>+</sup> T cells as well as significantly up regulated IL-19 and IL-24 gene expression, suggesting that IL-10 regulates IL-19 and IL-24 expression in T cells. In addition, IL-1β and IL-23 blockade also induced a diminution in the frequency of IL-19<sup>+</sup> and IL-24<sup>+</sup> T cells, indicating a novel role for these cytokines in the induction of IL-19 and IL-24 expressing T cells. Finally, elimination of infection resulted in significantly decreased frequencies of antigen – specific CD4<sup>+</sup> T cells expressing IL-10, IL-19 and IL-24.</p></sec><sec><title>Conclusions</title><p>Our findings, therefore, suggest that IL-19 and IL-24 are associated with the regulation of immune responses in active filarial infection and potentially with protection against development of pathology, while IL-26 is predominantly associated with pathology in LF.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Babu, S" uniqKey="Babu S">S Babu</name></author><author><name sortKey="Nutman, Tb" uniqKey="Nutman T">TB Nutman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nutman, Tb" uniqKey="Nutman T">TB Nutman</name></author><author><name sortKey="Kumaraswami, V" uniqKey="Kumaraswami V">V Kumaraswami</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="King, Cl" uniqKey="King C">CL King</name></author><author><name sortKey="Nutman, Tb" uniqKey="Nutman T">TB Nutman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Babu, S" uniqKey="Babu S">S Babu</name></author><author><name sortKey="Blauvelt, Cp" uniqKey="Blauvelt C">CP Blauvelt</name></author><author><name sortKey="Kumaraswami, V" uniqKey="Kumaraswami V">V Kumaraswami</name></author><author><name sortKey="Nutman, Tb" uniqKey="Nutman T">TB Nutman</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Nutman, Tb" uniqKey="Nutman T">TB Nutman</name></author><author><name sortKey="Kumaraswami, V" uniqKey="Kumaraswami V">V Kumaraswami</name></author><author><name sortKey="Ottesen, Ea" uniqKey="Ottesen E">EA Ottesen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Babu, S" uniqKey="Babu S">S Babu</name></author><author><name sortKey="Bhat, Sq" uniqKey="Bhat S">SQ 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Negl Trop Dis</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Negl Trop Dis</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosntds</journal-id><journal-title-group><journal-title>PLoS Neglected Tropical Diseases</journal-title></journal-title-group><issn pub-type="ppub">1935-2727</issn><issn pub-type="epub">1935-2735</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24699268</article-id><article-id pub-id-type="pmc">3974669</article-id><article-id pub-id-type="publisher-id">PNTD-D-13-01225</article-id><article-id pub-id-type="doi">10.1371/journal.pntd.0002762</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology and Life Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Clinical Immunology</subject><subj-group><subject>Immunomodulation</subject></subj-group></subj-group><subj-group><subject>Immune Response</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine and Health Sciences</subject><subj-group><subject>Infectious Diseases</subject></subj-group><subj-group><subject>Parasitic Diseases</subject><subj-group><subject>Helminth Infections</subject><subj-group><subject>Filariasis</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Expansion of Parasite-Specific CD4<sup>+</sup> and CD8<sup>+</sup> T Cells Expressing IL-10 Superfamily Cytokine Members and Their Regulation in Human Lymphatic Filariasis</article-title><alt-title alt-title-type="running-head">IL-19, IL-24 and IL-26 in Lymphatic Filariasis</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Anuradha</surname><given-names>Rajamanickam</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>George</surname><given-names>Parakkal Jovvian</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hanna</surname><given-names>Luke E.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kumaran</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chandrasekaran</surname><given-names>Vedachalam</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nutman</surname><given-names>Thomas B.</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Babu</surname><given-names>Subash</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>National Institutes of Health—International Center for Excellence in Research, Chennai, India</addr-line></aff><aff id="aff2"><label>2</label><addr-line>National Institute for Research in Tuberculosis, Chennai, India</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Specht</surname><given-names>Sabine</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University Clinic Bonn, Germany</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>sbabu@mail.nih.gov</email></corresp><fn fn-type="conflict"><p>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: TBN SB. Performed the experiments: RA PJG. Analyzed the data: RA PJG. Contributed reagents/materials/analysis tools: LEH PK VC. Wrote the paper: TBN SB.</p></fn></author-notes><pub-date pub-type="collection"><month>4</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>3</day><month>4</month><year>2014</year></pub-date><volume>8</volume><issue>4</issue><elocation-id>e2762</elocation-id><history><date date-type="received"><day>13</day><month>8</month><year>2013</year></date><date date-type="accepted"><day>16</day><month>2</month><year>2014</year></date></history><permissions><copyright-year>2014</copyright-year><license><license-p>This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.</license-p></license></permissions><abstract><sec><title>Background</title><p>Lymphatic filariasis (LF) is known to be associated with an increased production of IL-10. The role of the other IL-10 family members in the pathogenesis of infection and/or disease is not known.</p></sec><sec><title>Methodology/Principal Findings</title><p>We examined the expression patterns of IL-10 family members – IL-19, IL-24 and IL-26 in LF. We demonstrate that both CD4<sup>+</sup> and CD8<sup>+</sup> T cells express IL-19, IL-24 and IL-26 and that the frequency of CD4<sup>+</sup> T cells expressing IL-19 and IL-24 (as well as IL-10) is significantly increased at baseline and following filarial antigen stimulation in patients with LF in comparison to individuals with filarial lymphedema and uninfected individuals. This CD4<sup>+</sup> T cell expression pattern was associated with increased production of IL-19 and IL-24 by filarial – antigen stimulated PBMC. Moreover, the frequency of CD4<sup>+</sup> and CD8<sup>+</sup> T cells expressing IL-26 was significantly increased following filarial antigen stimulation in filarial lymphedema individuals. Interestingly, IL-10 blockade resulted in diminished frequencies of IL-19<sup>+</sup> and IL-24<sup>+</sup> T cells, whereas the addition of recombinant IL-10 resulted in significantly increased frequency of IL-19<sup>+</sup> and IL-24<sup>+</sup> T cells as well as significantly up regulated IL-19 and IL-24 gene expression, suggesting that IL-10 regulates IL-19 and IL-24 expression in T cells. In addition, IL-1β and IL-23 blockade also induced a diminution in the frequency of IL-19<sup>+</sup> and IL-24<sup>+</sup> T cells, indicating a novel role for these cytokines in the induction of IL-19 and IL-24 expressing T cells. Finally, elimination of infection resulted in significantly decreased frequencies of antigen – specific CD4<sup>+</sup> T cells expressing IL-10, IL-19 and IL-24.</p></sec><sec><title>Conclusions</title><p>Our findings, therefore, suggest that IL-19 and IL-24 are associated with the regulation of immune responses in active filarial infection and potentially with protection against development of pathology, while IL-26 is predominantly associated with pathology in LF.</p></sec></abstract><abstract abstract-type="summary"><title>Author Summary</title><p>Lymphatic filariasis afflicts over 120 million people worldwide. While the infection is mostly clinically asymptomatic, approximately 40 million people suffer from overt, morbid clinical pathology, characterized by swelling of the scrotal area and lower limbs (hydrocele and lymphedema). Host immunologic factors that influence the pathogenesis of disease in these individuals are not completely understood. CD4<sup>+</sup> and CD8<sup>+</sup> T cells are known to play a role in promoting pathogenesis through the secretion of pro-inflammatory cytokines, while IL-10 is known to play an important role in dampening inflammation. IL-10 belongs to a family of cytokines that include IL-19, IL-24 and IL-26, known as the IL-10 superfamily. We investigated whether these cytokines have a function similar to IL-10 in individuals with asymptomatic infection and no clinical pathology and those with overt, clinical pathology. We first identify that CD4<sup>+</sup> and CD8<sup>+</sup> T cells produce these cytokines. We next identify a significant association of IL-19 and IL-24 secreting T cells with asymptomatic infection. IL-26 secreting T cells, in contrast, appear to be significantly associated with the presence of lymphatic pathology in filarial infection. Therefore, we have uncovered a potentially new regulatory pathway involving the IL-10 superfamily cytokines in filarial infections.</p></abstract><funding-group><funding-statement>This work was supported by the Division of Intramural Research, NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="13"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Inde</li><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="Inde"><noRegion><name sortKey="Anuradha, Rajamanickam" sort="Anuradha, Rajamanickam" uniqKey="Anuradha R" first="Rajamanickam" last="Anuradha">Rajamanickam Anuradha</name></noRegion><name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</name><name sortKey="Chandrasekaran, Vedachalam" sort="Chandrasekaran, Vedachalam" uniqKey="Chandrasekaran V" first="Vedachalam" last="Chandrasekaran">Vedachalam Chandrasekaran</name><name sortKey="George, Parakkal Jovvian" sort="George, Parakkal Jovvian" uniqKey="George P" first="Parakkal Jovvian" last="George">Parakkal Jovvian George</name><name sortKey="Hanna, Luke E" sort="Hanna, Luke E" uniqKey="Hanna L" first="Luke E." last="Hanna">Luke E. Hanna</name><name sortKey="Kumaran, Paul" sort="Kumaran, Paul" uniqKey="Kumaran P" first="Paul" last="Kumaran">Paul Kumaran</name></country><country name="États-Unis"><region name="Maryland"><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name></region><name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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