T regulatory cells are critical for the maintenance, anamnestic expansion and protection elicited by vaccine-induced CD8 T cells.

T regulatory (Treg) cells are critical for preventing autoimmunity and suppressing immune responses during cancer and chronic infection. However, the role of Treg cells in the generation of vaccine-induced immune memory remains ill-defined. Using the mouse model of lymphocytic choriomeningitis virus (LCMV) infection, we demonstrate that transient absence of Treg cells during effector to memory CD8 T-cell transition results in a permanent impairment in the maintenance, function and recall capacity of CD8 T cells. Memory CD8 T cells in mice that were transiently depleted of Treg cells exhibited defective up-regulation of memory markers with a significant decrease in polyfunctionality. However, Treg-depleted mice showed no significant change in CD4 T-cell responses, and antibody levels relative to control. Altogether, this study evaluates the role of Treg cells in the formation of immune memory and demonstrates an important role for Treg cells in promoting memory CD8 T-cell differentiation and vaccine-induced immune protection against intracellular pathogens.