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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigen-Presenting Cells / immunology
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Antigens, Fungal / immunology
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Candida albicans / immunology
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Cells, Cultured
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Humans
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Immunologic Memory / drug effects
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Immunologic Memory / immunology
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Interferon-gamma / antagonists & inhibitors*
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Interferon-gamma / metabolism
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Interleukin-10 / pharmacology*
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Interleukin-17 / antagonists & inhibitors
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Interleukin-17 / biosynthesis*
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Interleukin-2 / immunology
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Interleukin-2 / metabolism
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Neutrophils / drug effects
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Neutrophils / immunology
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Protein Tyrosine Phosphatase, Non-Receptor Type 6 / immunology
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Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
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Receptors, Antigen, T-Cell / agonists
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Receptors, Antigen, T-Cell / metabolism*
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STAT3 Transcription Factor / metabolism
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins / metabolism
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T-Lymphocyte Subsets / drug effects*
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T-Lymphocyte Subsets / immunology
Substances
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Antigens, Fungal
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IL2 protein, human
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Interleukin-17
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Interleukin-2
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Receptors, Antigen, T-Cell
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SOCS3 protein, human
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STAT3 Transcription Factor
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STAT3 protein, human
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins
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Interleukin-10
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Interferon-gamma
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 6