title: IL-10 interferes directly with TCR-induced IFN-gamma but not IL-17 production in memory T cells.
abstract: IL-10 is a potent immunoregulatory and anti-inflammatory cytokine. However, therapeutic trials in chronic inflammation have been largely disappointing. It is well established that IL-10 can inhibit Th1 and Th2 cytokine production via indirect effects on APC. Less data are available about the influence of IL-10 on IL-17 production, a cytokine which has been recently linked to chronic inflammation. Furthermore, there are only few reports about a direct effect of IL-10 on T cells. We demonstrate here that IL-10 can directly interfere with TCR-induced IFN-gamma production in freshly isolated memory T cells in the absence of APC. This effect was independent of the previously described effects of IL-10 on T cells, namely inhibition of IL-2 production and inhibition of CD28 signaling. In contrast, IL-10 did not affect anti-CD3/anti-CD28-induced IL-17 production from memory T cells even in the presence of APC. This might have implications for the interpretation of therapeutic trials in patients with chronic inflammation where Th17 cells contribute to pathogenesis.
authors.affiliation: Institute of Medical Immunology, Charité, Humboldt-University, Berlin, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Naundorf
authors.forename: Martina
authors.initials: M
authors.lastname: Schröder
authors.forename: Conny
authors.initials: C
authors.lastname: Höflich
authors.forename: Nimisha
authors.initials: N
authors.lastname: Suman
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Gerald
authors.initials: G
authors.lastname: Grütz
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D000946:Antigens, Fungal / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology
chemical_list: D000946:Antigens, Fungal; C508594:IL2 protein, human; D020381:Interleukin-17; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10; D007371:Interferon-gamma; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6