FoxP3+ regulatory CD4 T cells control the generation of functional CD8 memory

During the primary immune response, CD8 memory emerges from an environment of strong immune activation. The FoxP3+ regulatory CD4 T-cell subset (Treg) is known as a key suppressive component of the immune system. Here we report that Tregs are required for the generation of functional CD8 memory. In the absence of Tregs during priming, the resulting memory cells proliferate poorly and fail to differentiate into functional cytotoxic secondary effectors following antigen reactivation. We find that the Tregs act early, during the expansion phase of primary CD8 effectors, by fine tuning interleukin-2 exposure of CD8 memory precursors. This crucial new role of Tregs has implications for optimal vaccine development. The role of CD4+ T cells in the generation of memory CD8+ T cells is not fully understood. In this study, the exposure of CD8 memory precursors to interleukin-2 during early antigen priming is shown to be controlled by FoxP3+ regulatory CD4+T cells, resulting in the production of functional memory cells.