T cell-intrinsic role of IL-6 signaling in primary and memory responses

Innate immune recognition is critical for the induction of adaptive immune responses; however the underlying mechanisms remain incompletely understood. Here, we demonstrate that T cell-specific deletion of the IL-6 receptor a chain (IL-6Ra) results in impaired Th1 and Th17 T cell responses in vivo, and a defect in the Tfh function. Depletion of Tregs in these mice rescued the Th1 but not the Th17 response. Our data suggest that IL-6 signaling in effector T cells is required to overcome Treg-mediated suppression in vivo. We show that IL-6 cooperates with IL-1|3 to block the suppressive effect of Tregs on CD4+ T cells, at least in part by controlling their responsiveness to IL-2. In addition, although IL-6Ra-deficient T cells mount normal primary Th1 responses in the absence of Tregs, they fail to mature into functional memory cells, demonstrating a key role for IL-6 in CD4⁺ T cell memory formation.