CD4+ T cell-derived IL-10 is independent of IL-27 signaling in a recall response. (CCR3P.220)

Abstract

Abstract Surviving influenza infection requires a careful balance of pro-inflammatory signals that promote viral clearance and anti-inflammatory signals that prevent immunopathology. IL-10 is a potent immunosuppressive cytokine that is essential to this balance. Evidence suggests that in CD4+ T cells, IL-10 expression is critically dependent on IL-27 signaling. Here we show in vitro and in vivo that CD4+ cells downregulate gp130, the signal transduction component of the IL-27 receptor, upon activation. Gp130 expression remains low throughout CD4+ T cell contraction and memory, and renders the T cells non-responsive to IL-27 stimulation. Despite this, during secondary activation effector CD4+ T cells express IL-10 at a level equivalent to their primary effector counterparts. Cells genetically deficient for il27ra also fail to express IL-10 during primary activation but are equivalent to wildtype cells during a secondary response. Together our data highlight an IL-27 independent mechanism of IL-10 regulation that is unique to secondary CD4+ T cell activation, and plays a decisive role in the balance between effective immunity and immunopathology during influenza-induced respiratory disease.