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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 : 005C11

Parasite 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 :

RBID : PMC:3764459

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English descriptors

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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<term>Interleukine-4 (métabolisme)</term>
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<term>Interleukine-9 (immunologie)</term>
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<term>Lymphocytes T CD4+ (métabolisme)</term>
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<term>Facteur de croissance transformant bêta</term>
<term>Filariose lymphatique</term>
<term>Interleukine-1</term>
<term>Interleukine-10</term>
<term>Interleukine-4</term>
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<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>
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<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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<nlm:aff id="A1">National Institutes of Health—International Center for Excellence in Research, Chennai, India</nlm:aff>
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<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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<nlm:aff id="A2">National Institute for Research in Tuberculosis, Chennai, India</nlm:aff>
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<name sortKey="Chandrasekaran, Vedachalam" sort="Chandrasekaran, Vedachalam" uniqKey="Chandrasekaran V" first="Vedachalam" last="Chandrasekaran">Vedachalam Chandrasekaran</name>
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<nlm:aff id="A2">National Institute for Research in Tuberculosis, Chennai, India</nlm:aff>
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<name sortKey="Kumaran, Paul" sort="Kumaran, Paul" uniqKey="Kumaran P" first="Paul" last="Kumaran">Paul Kumaran</name>
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<nlm:aff id="A2">National Institute for Research in Tuberculosis, Chennai, India</nlm:aff>
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<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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<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>
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<name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</name>
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<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>
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<term>Elephantiasis, Filarial (metabolism)</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Humans</term>
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<term>Interleukin-4 (metabolism)</term>
<term>Interleukin-9 (biosynthesis)</term>
<term>Interleukin-9 (immunology)</term>
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<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 (immunologie)</term>
<term>Facteur de croissance transformant bêta (métabolisme)</term>
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<term>Filariose lymphatique (métabolisme)</term>
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<term>Interleukine-9 (immunologie)</term>
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<term>Sous-populations de lymphocytes T (métabolisme)</term>
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<term>Elephantiasis, Filarial</term>
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<term>CD4-Positive T-Lymphocytes</term>
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<term>Interleukin-1</term>
<term>Interleukin-4</term>
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<term>Enzyme-Linked Immunosorbent Assay</term>
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<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>
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