TLR2 engagement on memory CD8+ T cells improves their cytokine-mediated proliferation and IFN-γ secretion in the absence of Ag

Persistence of memory CD8(+) T cells is known to be largely controlled by common gamma chain cytokines, such as IL-2, IL-7 and IL-15. However, other molecules may be involved in this phenomenon. We show here that TLR2(-/-) mice have a decreased frequency of memory phenotype CD8(+) T cells when compared with WT mice. This prompted us to investigate the role of TLR2 in the homeostasis of memory CD8(+) T cells. We describe here a new TLR2-dependent mechanism which, in the absence of specific antigen, directly controls memory CD8(+) T-cell proliferation and IFN-gamma secretion. We demonstrate that TLR2 engagement on memory CD8(+) T cells increases their proliferation and expansion induced by IL-7 both in vitro and in vivo. We also show that TLR2 ligands act in synergy with IL-2 to induce IFN-gamma secretion in vitro. Both conclusions are obtained with spontaneously arising memory phenotype and antigen-specific memory CD8(+) T cells. Altogether, our data support the idea that continuous TLR2 signaling in response to microbial stimuli or endogenous danger signals might directly contribute to the maintenance of the diversity memory CD8(+) T cells in the organism.