Expansion of Parasite-Specific CD4+ and CD8+ T Cells Expressing IL-10 Superfamily Cytokine Members and Their Regulation in Human Lymphatic Filariasis
Identifieur interne : 002B00 ( Main/Exploration ); précédent : 002A99; suivant : 002B01Expansion 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.
Descripteurs français
- KwdFr :
- MESH :
- immunologie : Filariose lymphatique, Lymphocytes T CD4+, Lymphocytes T CD8+.
- sécrétion : Interleukines.
- Adulte, Adulte d'âge moyen, Animaux, Femelle, Humains, Jeune adulte, Mâle, Sujet âgé.
English descriptors
- KwdEn :
- MESH :
- chemical , secretion : Interleukins.
- immunology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Elephantiasis, Filarial.
- Adult, Aged, Animals, Female, Humans, Male, Middle Aged, Young Adult.
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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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><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>CD4-Positive T-Lymphocytes (immunology)</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Elephantiasis, Filarial (immunology)</term><term>Female</term><term>Humans</term><term>Interleukins (secretion)</term><term>Male</term><term>Middle Aged</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Animaux</term><term>Femelle</term><term>Filariose lymphatique (immunologie)</term><term>Humains</term><term>Interleukines (sécrétion)</term><term>Jeune adulte</term><term>Lymphocytes T CD4+ (immunologie)</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Mâle</term><term>Sujet âgé</term></keywords><keywords scheme="MESH" type="chemical" qualifier="secretion" xml:lang="en"><term>Interleukins</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Filariose lymphatique</term><term>Lymphocytes T CD4+</term><term>Lymphocytes T CD8+</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term><term>CD8-Positive T-Lymphocytes</term><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" qualifier="sécrétion" xml:lang="fr"><term>Interleukines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Animaux</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Mâle</term><term>Sujet âgé</term></keywords></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 Bhat</name></author><author><name sortKey="Pavan Kumar, N" uniqKey="Pavan Kumar N">N Pavan Kumar</name></author><author><name sortKey="Lipira, Ab" uniqKey="Lipira A">AB Lipira</name></author><author><name sortKey="Kumar, S" uniqKey="Kumar S">S Kumar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anuradha, R" uniqKey="Anuradha R">R Anuradha</name></author><author><name sortKey="George, Pj" uniqKey="George P">PJ George</name></author><author><name sortKey="Pavan Kumar, N" uniqKey="Pavan Kumar N">N Pavan Kumar</name></author><author><name sortKey="Fay, Mp" uniqKey="Fay M">MP Fay</name></author><author><name sortKey="Kumaraswami, V" uniqKey="Kumaraswami V">V Kumaraswami</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Metenou, S" uniqKey="Metenou S">S Metenou</name></author><author><name sortKey="Dembele, B" uniqKey="Dembele B">B Dembele</name></author><author><name sortKey="Konate, S" uniqKey="Konate S">S 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M" uniqKey="Kuwamura M">M Kuwamura</name></author><author><name sortKey="Yancopoulos, Gd" uniqKey="Yancopoulos G">GD Yancopoulos</name></author><author><name sortKey="Valenzuela, Dm" uniqKey="Valenzuela D">DM Valenzuela</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Azuma, Yt" uniqKey="Azuma Y">YT Azuma</name></author><author><name sortKey="Nakajima, H" uniqKey="Nakajima H">H Nakajima</name></author><author><name sortKey="Takeuchi, T" uniqKey="Takeuchi T">T Takeuchi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="England, Rn" uniqKey="England R">RN England</name></author><author><name sortKey="Autieri, Mv" uniqKey="Autieri M">MV Autieri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dambacher, J" uniqKey="Dambacher J">J Dambacher</name></author><author><name sortKey="Beigel, F" uniqKey="Beigel F">F Beigel</name></author><author><name sortKey="Zitzmann, K" uniqKey="Zitzmann K">K Zitzmann</name></author><author><name sortKey="De Toni, En" uniqKey="De Toni E">EN De Toni</name></author><author><name sortKey="Goke, B" uniqKey="Goke B">B Goke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Jr" uniqKey="Chan J">JR Chan</name></author><author><name sortKey="Blumenschein, W" uniqKey="Blumenschein W">W Blumenschein</name></author><author><name sortKey="Murphy, E" uniqKey="Murphy E">E Murphy</name></author><author><name sortKey="Diveu, C" uniqKey="Diveu C">C Diveu</name></author><author><name sortKey="Wiekowski, M" uniqKey="Wiekowski M">M Wiekowski</name></author></analytic></biblStruct></listBibl></div1></back></TEI><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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