title: IL-4-, TGF-β-, and IL-1-dependent expansion of parasite antigen-specific Th9 cells is associated with clinical pathology in human lymphatic filariasis.
abstract: 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.
authors.affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai 600031, India.
authors.forename: Rajamanickam
authors.initials: R
authors.lastname: Anuradha
authors.forename: Parakkal Jovvian
authors.initials: PJ
authors.lastname: George
authors.forename: Luke E
authors.initials: LE
authors.lastname: Hanna
authors.forename: Vedachalam
authors.initials: V
authors.lastname: Chandrasekaran
authors.forename: Paul
authors.initials: P
authors.lastname: Kumaran
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004605:Elephantiasis, Filarial / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D016906:Interleukin-9 / Q000096:biosynthesis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: C508598:IL4 protein, human; D007375:Interleukin-1; D016906:Interleukin-9; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4
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