A persistent loss of cytokine responsiveness defines CD8+ memory T cell function (150.2)

Abstract

Abstract Cytokines are soluble signaling molecules that orchestrate immune responses, regulating both immune protection and immunopathology. T cell differentiation is characterized by distinctive changes in cytokine production, but less is known about concomitant changes in cytokine responsiveness. Here we report that CD8+ T cell differentiation imposes permanent alterations in the cytokine receptor repertoire. We show that influenza virus-specific CD8+ memory T cells in both humans and mice lose responsiveness to interleukin (IL)-27. This loss is due to persistent downregulation of the shared gp130 cytokine receptor chain on effector and memory T cells and occurs as a direct consequence of antigenic stimulation. Loss of IL-27 responsiveness renders CD8+ memory T cells deficient in their expression of the immunosuppressive cytokine IL-10 during recall responses. Together our data reveal a previously unappreciated feature of CD8+ T cell differentiation, in which the selective and persistent loss of specific cytokine receptors defines the functional potential of memory cells during rechallenge. The altered cytokine responsiveness of effector and memory T cells has fundamental implications for the functional manipulation of these cells in vivo.