Parasite antigen-specific, IL-4-, TGFβ- and IL-1- dependent expansion of Th9 cells is associated with clinical pathology in human lymphatic filariasis
Identifieur interne : 005C10 ( Ncbi/Merge ); précédent : 005C09; suivant : 005C11Parasite antigen-specific, IL-4-, TGFβ- and IL-1- dependent expansion of Th9 cells is associated with clinical pathology in human lymphatic filariasis
Auteurs : Rajamanickam Anuradha [Inde] ; Parakkal Jovvian George [Inde] ; Luke E. Hanna [Inde] ; Vedachalam Chandrasekaran [Inde] ; Paul Kumaran [Inde] ; Thomas B. Nutman [États-Unis] ; Subash Babu [Inde, États-Unis]Source :
- Journal of immunology (Baltimore, Md. : 1950) [ 0022-1767 ] ; 2013.
Descripteurs français
- KwdFr :
- Facteur de croissance transformant bêta (immunologie), Facteur de croissance transformant bêta (métabolisme), Filariose lymphatique (immunologie), Filariose lymphatique (métabolisme), Humains, Interleukine-1 (immunologie), Interleukine-1 (métabolisme), Interleukine-10 (biosynthèse), Interleukine-10 (immunologie), Interleukine-4 (immunologie), Interleukine-4 (métabolisme), Interleukine-9 (biosynthèse), Interleukine-9 (immunologie), Lymphocytes T CD4+ (immunologie), Lymphocytes T CD4+ (métabolisme), Sous-populations de lymphocytes T (immunologie), Sous-populations de lymphocytes T (métabolisme), Test ELISA.
- MESH :
- biosynthèse : Interleukine-10, Interleukine-9.
- immunologie : Facteur de croissance transformant bêta, Filariose lymphatique, Interleukine-1, Interleukine-10, Interleukine-4, Interleukine-9, Lymphocytes T CD4+, Sous-populations de lymphocytes T.
- métabolisme : Facteur de croissance transformant bêta, Filariose lymphatique, Interleukine-1, Interleukine-4, Lymphocytes T CD4+, Sous-populations de lymphocytes T.
- Humains, Test ELISA.
English descriptors
- KwdEn :
- CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (metabolism), Elephantiasis, Filarial (immunology), Elephantiasis, Filarial (metabolism), Enzyme-Linked Immunosorbent Assay, Humans, Interleukin-1 (immunology), Interleukin-1 (metabolism), Interleukin-10 (biosynthesis), Interleukin-10 (immunology), Interleukin-4 (immunology), Interleukin-4 (metabolism), Interleukin-9 (biosynthesis), Interleukin-9 (immunology), T-Lymphocyte Subsets (immunology), T-Lymphocyte Subsets (metabolism), Transforming Growth Factor beta (immunology), Transforming Growth Factor beta (metabolism).
- MESH :
- chemical , biosynthesis : Interleukin-10, Interleukin-9.
- chemical , immunology : Interleukin-1, Interleukin-10, Interleukin-4, Interleukin-9, Transforming Growth Factor beta.
- immunology : CD4-Positive T-Lymphocytes, Elephantiasis, Filarial, T-Lymphocyte Subsets.
- metabolism : CD4-Positive T-Lymphocytes, Elephantiasis, Filarial, Interleukin-1, Interleukin-4, T-Lymphocyte Subsets, Transforming Growth Factor beta.
- Enzyme-Linked Immunosorbent Assay, Humans.
Abstract
Th9 cells are a subset of CD4+ T cells, shown to be important in allergy, autoimmunity and anti-tumor responses. However, their role in human infectious diseases has not been explored in detail. We identified a population of IL-9 and IL-10 co-expressing cells (lacking IL-4 expression) in normal individuals that respond to antigenic and mitogenic stimulation but are distinct from IL-9+ Th2 cells. We also demonstrate that these Th9 cells exhibit antigen –specific expansion in a chronic helminth infection (lymphatic filariasis). Comparison of Th9 responses reveals that individuals with pathology associated with filarial infection exhibit significantly expanded frequencies of filarial antigen induced Th9 cells but not of IL9+Th2 cells in comparison to filarial-infected individuals without associated disease. Moreover, the per cell production of IL-9 is significantly higher in Th9 cells compared to IL9+Th2 cells, indicating that the Th9 cells are the predominant CD4+ T cell subset producing IL-9 in the context of human infection. This expansion was reflected in elevated antigen stimulated IL-9 cytokine levels in whole blood culture supernatants. Finally, the frequencies of Th9 cells correlated positively with the severity of lymphedema (and presumed inflammation) in filarial diseased individuals. This expansion of Th9 cells was dependent on IL-4, TGFβ and IL-1 in vitro. We have therefore a identified an important human CD4+ T cell subpopulation co – expressing IL-9 and IL-10 but not IL-4 that is whose expansion is associated with disease in chronic lymphatic filariasis and could potentially play an important role in the pathogenesis of other inflammatory disorders.
Url:
DOI: 10.4049/jimmunol.1300911
PubMed: 23913964
PubMed Central: 3764459
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PMC:3764459Le document en format XML
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<term>CD4-Positive T-Lymphocytes (metabolism)</term>
<term>Elephantiasis, Filarial (immunology)</term>
<term>Elephantiasis, Filarial (metabolism)</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Humans</term>
<term>Interleukin-1 (immunology)</term>
<term>Interleukin-1 (metabolism)</term>
<term>Interleukin-10 (biosynthesis)</term>
<term>Interleukin-10 (immunology)</term>
<term>Interleukin-4 (immunology)</term>
<term>Interleukin-4 (metabolism)</term>
<term>Interleukin-9 (biosynthesis)</term>
<term>Interleukin-9 (immunology)</term>
<term>T-Lymphocyte Subsets (immunology)</term>
<term>T-Lymphocyte Subsets (metabolism)</term>
<term>Transforming Growth Factor beta (immunology)</term>
<term>Transforming Growth Factor beta (metabolism)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Facteur de croissance transformant bêta (immunologie)</term>
<term>Facteur de croissance transformant bêta (métabolisme)</term>
<term>Filariose lymphatique (immunologie)</term>
<term>Filariose lymphatique (métabolisme)</term>
<term>Humains</term>
<term>Interleukine-1 (immunologie)</term>
<term>Interleukine-1 (métabolisme)</term>
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<term>Interleukine-10 (immunologie)</term>
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<term>Interleukine-9 (biosynthèse)</term>
<term>Interleukine-9 (immunologie)</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD4+ (métabolisme)</term>
<term>Sous-populations de lymphocytes T (immunologie)</term>
<term>Sous-populations de lymphocytes T (métabolisme)</term>
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<term>Interleukin-4</term>
<term>Interleukin-9</term>
<term>Transforming Growth Factor beta</term>
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<term>Interleukine-9</term>
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<term>Filariose lymphatique</term>
<term>Interleukine-1</term>
<term>Interleukine-10</term>
<term>Interleukine-4</term>
<term>Interleukine-9</term>
<term>Lymphocytes T CD4+</term>
<term>Sous-populations de lymphocytes T</term>
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<term>Interleukin-1</term>
<term>Interleukin-4</term>
<term>T-Lymphocyte Subsets</term>
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<front><div type="abstract" xml:lang="en"><p id="P1">Th9 cells are a subset of CD4<sup>+</sup>
T cells, shown to be important in allergy, autoimmunity and anti-tumor responses. However, their role in human infectious diseases has not been explored in detail. We identified a population of IL-9 and IL-10 co-expressing cells (lacking IL-4 expression) in normal individuals that respond to antigenic and mitogenic stimulation but are distinct from IL-9<sup>+</sup>
Th2 cells. We also demonstrate that these Th9 cells exhibit antigen –specific expansion in a chronic helminth infection (lymphatic filariasis). Comparison of Th9 responses reveals that individuals with pathology associated with filarial infection exhibit significantly expanded frequencies of filarial antigen induced Th9 cells but not of IL9<sup>+</sup>
Th2 cells in comparison to filarial-infected individuals without associated disease. Moreover, the per cell production of IL-9 is significantly higher in Th9 cells compared to IL9<sup>+</sup>
Th2 cells, indicating that the Th9 cells are the predominant CD4<sup>+</sup>
T cell subset producing IL-9 in the context of human infection. This expansion was reflected in elevated antigen stimulated IL-9 cytokine levels in whole blood culture supernatants. Finally, the frequencies of Th9 cells correlated positively with the severity of lymphedema (and presumed inflammation) in filarial diseased individuals. This expansion of Th9 cells was dependent on IL-4, TGFβ and IL-1 in vitro. We have therefore a identified an important human CD4<sup>+</sup>
T cell subpopulation co – expressing IL-9 and IL-10 but not IL-4 that is whose expansion is associated with disease in chronic lymphatic filariasis and could potentially play an important role in the pathogenesis of other inflammatory disorders.</p>
</div>
</front>
</TEI>
<double pmid="23913964"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Parasite antigen-specific, IL-4-, TGFβ- and IL-1- dependent expansion of Th9 cells is associated with clinical pathology in human lymphatic filariasis</title>
<author><name sortKey="Anuradha, Rajamanickam" sort="Anuradha, Rajamanickam" uniqKey="Anuradha R" first="Rajamanickam" last="Anuradha">Rajamanickam Anuradha</name>
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<author><name sortKey="Chandrasekaran, Vedachalam" sort="Chandrasekaran, Vedachalam" uniqKey="Chandrasekaran V" first="Vedachalam" last="Chandrasekaran">Vedachalam Chandrasekaran</name>
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<author><name sortKey="Kumaran, Paul" sort="Kumaran, Paul" uniqKey="Kumaran P" first="Paul" last="Kumaran">Paul Kumaran</name>
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<author><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name>
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<wicri:regionArea>Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Parasite antigen-specific, IL-4-, TGFβ- and IL-1- dependent expansion of Th9 cells is associated with clinical pathology 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="A1">National Institutes of Health—International Center for Excellence in Research, Chennai, India</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="A1">National Institutes of Health—International Center for Excellence in Research, Chennai, India</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="A2">National Institute for Research in Tuberculosis, Chennai, India</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="A2">National Institute for Research in Tuberculosis, Chennai, India</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="A2">National Institute for Research in Tuberculosis, Chennai, India</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="A3">Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America</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>
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<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="A1">National Institutes of Health—International Center for Excellence in Research, Chennai, India</nlm:aff>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>National Institutes of Health—International Center for Excellence in Research, Chennai</wicri:regionArea>
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<affiliation wicri:level="2"><nlm:aff id="A3">Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America</nlm:aff>
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<front><div type="abstract" xml:lang="en"><p id="P1">Th9 cells are a subset of CD4<sup>+</sup>
T cells, shown to be important in allergy, autoimmunity and anti-tumor responses. However, their role in human infectious diseases has not been explored in detail. We identified a population of IL-9 and IL-10 co-expressing cells (lacking IL-4 expression) in normal individuals that respond to antigenic and mitogenic stimulation but are distinct from IL-9<sup>+</sup>
Th2 cells. We also demonstrate that these Th9 cells exhibit antigen –specific expansion in a chronic helminth infection (lymphatic filariasis). Comparison of Th9 responses reveals that individuals with pathology associated with filarial infection exhibit significantly expanded frequencies of filarial antigen induced Th9 cells but not of IL9<sup>+</sup>
Th2 cells in comparison to filarial-infected individuals without associated disease. Moreover, the per cell production of IL-9 is significantly higher in Th9 cells compared to IL9<sup>+</sup>
Th2 cells, indicating that the Th9 cells are the predominant CD4<sup>+</sup>
T cell subset producing IL-9 in the context of human infection. This expansion was reflected in elevated antigen stimulated IL-9 cytokine levels in whole blood culture supernatants. Finally, the frequencies of Th9 cells correlated positively with the severity of lymphedema (and presumed inflammation) in filarial diseased individuals. This expansion of Th9 cells was dependent on IL-4, TGFβ and IL-1 in vitro. We have therefore a identified an important human CD4<sup>+</sup>
T cell subpopulation co – expressing IL-9 and IL-10 but not IL-4 that is whose expansion is associated with disease in chronic lymphatic filariasis and could potentially play an important role in the pathogenesis of other inflammatory disorders.</p>
</div>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">IL-4-, TGF-β-, and IL-1-dependent expansion of parasite antigen-specific Th9 cells is associated with clinical pathology in human lymphatic filariasis.</title>
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<author><name sortKey="George, Parakkal Jovvian" sort="George, Parakkal Jovvian" uniqKey="George P" first="Parakkal Jovvian" last="George">Parakkal Jovvian George</name>
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<author><name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</name>
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<author><name sortKey="Anuradha, Rajamanickam" sort="Anuradha, Rajamanickam" uniqKey="Anuradha R" first="Rajamanickam" last="Anuradha">Rajamanickam Anuradha</name>
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<author><name sortKey="George, Parakkal Jovvian" sort="George, Parakkal Jovvian" uniqKey="George P" first="Parakkal Jovvian" last="George">Parakkal Jovvian George</name>
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<author><name sortKey="Hanna, Luke E" sort="Hanna, Luke E" uniqKey="Hanna L" first="Luke E" last="Hanna">Luke E. Hanna</name>
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<author><name sortKey="Chandrasekaran, Vedachalam" sort="Chandrasekaran, Vedachalam" uniqKey="Chandrasekaran V" first="Vedachalam" last="Chandrasekaran">Vedachalam Chandrasekaran</name>
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<term>Elephantiasis, Filarial (immunology)</term>
<term>Elephantiasis, Filarial (metabolism)</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Humans</term>
<term>Interleukin-1 (immunology)</term>
<term>Interleukin-1 (metabolism)</term>
<term>Interleukin-10 (biosynthesis)</term>
<term>Interleukin-10 (immunology)</term>
<term>Interleukin-4 (immunology)</term>
<term>Interleukin-4 (metabolism)</term>
<term>Interleukin-9 (biosynthesis)</term>
<term>Interleukin-9 (immunology)</term>
<term>T-Lymphocyte Subsets (immunology)</term>
<term>T-Lymphocyte Subsets (metabolism)</term>
<term>Transforming Growth Factor beta (immunology)</term>
<term>Transforming Growth Factor beta (metabolism)</term>
</keywords>
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<term>Facteur de croissance transformant bêta (métabolisme)</term>
<term>Filariose lymphatique (immunologie)</term>
<term>Filariose lymphatique (métabolisme)</term>
<term>Humains</term>
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<term>Interleukine-1 (métabolisme)</term>
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<term>Interleukine-10 (immunologie)</term>
<term>Interleukine-4 (immunologie)</term>
<term>Interleukine-4 (métabolisme)</term>
<term>Interleukine-9 (biosynthèse)</term>
<term>Interleukine-9 (immunologie)</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD4+ (métabolisme)</term>
<term>Sous-populations de lymphocytes T (immunologie)</term>
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<term>Test ELISA</term>
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<term>Filariose lymphatique</term>
<term>Interleukine-1</term>
<term>Interleukine-10</term>
<term>Interleukine-4</term>
<term>Interleukine-9</term>
<term>Lymphocytes T CD4+</term>
<term>Sous-populations de lymphocytes T</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>Elephantiasis, Filarial</term>
<term>T-Lymphocyte Subsets</term>
</keywords>
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<front><div type="abstract" xml:lang="en">Th9 cells are a subset of CD4(+) T cells, shown to be important in allergy, autoimmunity, and antitumor responses; however, their role in human infectious diseases has not been explored in detail. We identified a population of IL-9 and IL-10 coexpressing cells (lacking IL-4 expression) in normal individuals. These cells respond to antigenic and mitogenic stimulation, but are distinct from IL-9(+) Th2 cells. We also demonstrate that these Th9 cells exhibit Ag-specific expansion in a chronic helminth infection (lymphatic filariasis). Comparison of Th9 responses reveals that individuals with pathology associated with filarial infection exhibit significantly expanded frequencies of filarial Ag-induced Th9 cells, but not of IL9(+)Th2 cells in comparison with filarial-infected individuals without associated disease. Moreover, the per cell production of IL-9 is significantly higher in Th9 cells compared with IL9(+)Th2 cells, indicating that the Th9 cells are the predominant CD4(+) T cell subset producing IL-9 in the context of human infection. This expansion was reflected in elevated Ag-stimulated IL-9 cytokine levels in whole blood culture supernatants. Finally, the frequencies of Th9 cells correlated positively with the severity of lymphedema (and presumed inflammation) in filarial-diseased individuals. This expansion of Th9 cells was dependent on IL-4, TGF-β, and IL-1 in vitro. We have therefore identified an important human CD4(+) T cell subpopulation coexpressing IL-9 and IL-10, but not IL-4, the expansion of which is associated with disease in chronic lymphatic filariasis and could potentially have an important role in the pathogenesis of other inflammatory disorders.</div>
</front>
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