Targeting the OX40 (CD134) co-stimulatory receptor enhances mucosal secondary memory CD8 T cells (P270) (75.7)

Abstract

Abstract The expansion and maintenance of poly-functional memory CD8 T cells (mCD8) that rapidly migrate to sites of viral replication is paramount for the development of effective mucosal vaccines. This concept is epitomized by the limited success of vaccines that utilize attenuated or replication defective virus strains incapable of promoting mCD8 T cells that persist at mucosal sites. Consequently, strategies that enhance both the number and functionality of mCD8 T cells have attracted increasing interest. Recent studies have shown that targeting of the OX40 co-stimulatory receptor can promote primary mucosal CD8 T cell memory following infection with virulent and attenuated pox-virus vaccine strains. However, the ability of OX40 co-stimulation to enhance the reactivation of secondary mCD8 T cells is unclear. To mimic a prime boost vaccination strategy we transferred virus specific mCD8 T cells into naïve mice that were later immunized via dermal scarification. We show that OX40 agonism 24 hours following vaccination enhances both the number of virus specific secondary effector mCD8 T cells, defined by their expression of KLRG, IL7-R, CD62L and CD27, located within the lung and their capacity to produce both TNFα and IFNγ. These data provide evidence that targeting OX40 at the same time as an antigen boost (secondary challenge) can expand the numbers of effector mCD8 T cells that are capable of residing within lung tissue and thus protect against mucosal viral infection.