Regulation of T cells and cytokines by the interleukin‐10 (IL‐10)‐family cytokines IL‐19, IL‐20, IL‐22, IL‐24 andIL‐26

The family of IL‐10‐related cytokines includes several human members, IL‐19, IL‐20, IL‐22, IL‐24 and IL‐26, and a series of herpesviral and poxviral paralogs. Some of these cytokines share common receptor subunits. In this study, we investigated the effects of these cytokines on naive T cell differentiation, antigen‐specific T cell suppression, survival ad expression of surface markers in comparison to IL‐10 and cytomegalovirus (CMV)‐IL‐10. Human CD45RA+ T cells were stimulated in the presence of IL‐10‐family cytokines in sequential 12‐day cycles. After three to four cycles of stimulation, IL‐10 and CMV‐IL‐10 led to increased IFN‐γ and IL‐10 but decreased IL‐4 and IL‐13. Interestingly, long‐term exposure of T cells to IL‐19, IL‐20 and IL‐22 down‐regulated IFN‐γ but up‐regulated IL‐4 and IL‐13 in T cells and supported the polarization of naive T cells to Th2‐like cells. In contrast, neutralization of endogenous IL‐22 activity by IL‐22‐binding protein decreased IL‐4, IL‐13 and IFN‐γ synthesis. The antigen‐specific suppressor activity of IL‐10 and CMV‐IL‐10 was not observed for any of the other IL‐10‐family cytokines. These data demonstrate that IL‐19, IL‐20 and IL‐22 may participate in T cell‐mediated diseases by distinct regulation of T cell cytokine profiles.

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