Functionally impaired memory CD8 T cells are generated after vesicular stomatitis virus infection (105.13)

Abstract

Intracellular pathogens are capable of inducing vigorous CD8 T cell responses. However, it is unclear whether all memory CD8 T cell populations are capable of providing robust protective immunity against secondary infection. While both vesicular stomatitis virus (VSV) and Listeria monocytogenes infection result in the generation of large memory CD8 T cell populations that are capable of rapid secondary expansion, only memory cells induced by L. monocytogenes were protective against secondary infection. The lack of protective immunity after VSV priming correlated with expression of PD-1 on memory CD8 T cells. Importantly, mAb blockade of PD-1 at the time of re-challenge enhanced the ability of the VSV-induced memory CD8 T cell population to provide protective immunity. Moreover, overt activation of CD40, but not TLR9, signaling during priming enables the memory CD8 T cell population to provide strong protective immunity. CD40 signaling appears to alter the programming of the CD8 T cell response induced by VSV infection. Our data demonstrate that not all vaccine vectors are equal in their ability to generate highly protective memory CD8 T cell populations, even though they may generate memory population capable of undergoing robust secondary expansion. Thus, understanding how the CD40 signaling pathways regulate the generation of highly protective memory CD8 T cells will provide key insights into memory CD8 T cell biology and vaccine development.