Regulatory T Cells Increase the Avidity of Primary CD8+ T Cell Responses and Promote Memory

Although regulatory T cells (T-regs) are known to suppress self-reactive autoimmune responses, their role during T cell responses to nonself antigens is not well understood. We show that T-regs play a critical role during the priming of immune responses in mice. T-reg depletion induced the activation and expansion of a population of low-avidity CD8(+) T cells because of overproduction of CCL-3/4/5 chemokines, which stabilized the interactions between antigen-presenting dendritic cells and low-avidity T cells. In the absence of T-regs, the avidity of the primary immune response was impaired, which resulted in reduced memory to Listeria monocytogenes. These results suggest that T-regs are important regulators of the homeostasis of CD8(+) T cell priming and play a critical role in the induction of high-avidity primary responses and effective memory.