P171 Costimulation of IL-10 expression by type I interferon in human CD4 T cells

Abstract

Introduction Type I interferons (IFNs) exert a complex role in the immune system as shown by their capacity to drive anti- and proinflammatory responses. Previous studies have highlighted contrasting effects of IFNs in the development of CD4 T cell adaptive immune response. We have tested the hypothesis that IFN α may modulate the expression of anti- and proinflammatory cytokines IL-10 and IFN γ according to intrinsic parameters of T cell activation, e.g. T cell receptor (TCR) stimulation strength and CD28 costimulation, and to IFN dose. Methods The effect of IFN α was analyzed in whole blood samples from healthy donors and in peripheral nai¨ve CD4 T cells that were stimulated through TCR/CD3- and CD28-specific antibodies. Cytokine transcription and secretion were quantified by qPCR and Elisa. The differentiation of IL-10 and IFN γ -producing T cell subsets from nai¨ve CD4 T cells was examined by intracellular cytokine staining and flow cytometry. Results IFN α enhanced the early expression of IL-10 in a synergistic manner with TCR stimulation and promoted the differentiation of nai¨ve CD4 T cells into IL-10-producing T cell subsets, characterized as being mainly IL-10+ IFN γ -Tr1 cells (Tr1-IFN). These cells were efficiently generated in the presence of IFN α , provided that suitable TCR signal was elicited either through the help of CD28 or, in its absence, through strong TCR/CD3 stimulation. Conclusion We provide evidence for a potent TCR/IFN crosstalk promoting IL-10 expression. Our data support a two-step model in which IFN α costimulates TCR for IL-10 induction, which may be further amplified via an autocrine positive feedback loop. These novel findings may help understand immunoregulatory functions of type I interferons.