Eomesodermin promotes a central memory phenotype in CD8+ T cells through the induction of IL-10.

Abstract

Abstract Following an immune response, a fraction of antigen-specific T cells persist as memory cells. Of these, central memory CD8+ T cells (TCM), which express secondary lymphoid organ-homing molecules and self-renew efficiently, are critical for maintaining long term memory. High levels of the T-box transcription factor Eomesodermin (Eomes) are associated with the TCM phenotype, but the mechanisms by which Eomes controls different aspects of TCM function are poorly understood. Using Eomes-knockout (EKO) CD8+ T cells, we demonstrate that Eomes regulates the expression of a number of TCM-associated markers including Bcl6, Ly6C and CD62L. In addition, we found that Eomes promotes the expression of IL-10 in activated CD8+ T cells. Interestingly, the addition of exogenous IL-10 was sufficient to upregulate CD62L expression in WT cells. Taken together, our data suggest that Eomes uses IL-10 to promote at least part of the central memory phenotype in CD8+ T cells. Consistent with this model, we find that TCM are secreting IL-10 in vivo, without additional re-stimulation. These findings warrant a modified model of TCM differentiation which includes distinct roles for Eomes and IL-10 in a T cell-intrinsic program driving TCM formation.