The role of interleukin-10 (IL-10) in IL-15-mediated T-cell responses

Dieter Körholz, Ursula Banning, Halvard Bönig, Markus Grewe, Marion Schneider, Christine Mauz-Körholz, Anne Klein-Vehne, Jean Krutmann, Stephan Burdach

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Interleukin-15 (IL-15) is a potent T-cell stimulating factor, which has recently been used for pre-clinical in vivo immunotherapy. Here, the IL-15 effect on CD3-stimulated peripheral human T cells was investigated. IL-15 induced a significant T-cell proliferation and upregulated CD25 expression, IL-15 significantly enhanced T-cell production of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-10. Between 10- and 100-fold greater concentrations of IL-15 were necessary to reach a biological effect equivalent to that of IL-2. Blockade of IL-2 binding to the high-affinity IL- 2 receptor did not affect the IL-15 effects, suggesting that IL-15 did not act by inducing endogenous IL-2. Exogenously administered IL-10 significantly reduced the IL-15 and IL-2-mediated IFN γ and TNF-α production, whereas T- cell proliferation and CD25 expression were not affected. The inhibitory effects of exogenously administered IL-10 on T-cell cytokine production appeared indirect, and are likely secondary to decreased IL-12 production by accessory cells. Inhibition of endogenous IL-10 binding to the IL-10 receptor significantly increased IFN-γ and TNF-α release from T cells. These data suggest that endogenous IL-10 can regulate activated T-cell production of IFN-γ and TNF-α via a paracrine negative feedback loop. The observations of this study could be of relevance for the therapeutic use of IL-15 in vivo.

Original languageEnglish
Pages (from-to)4513-4521
Number of pages9
JournalBlood
Volume90
Issue number11
DOIs
StatePublished - 1 Dec 1997

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