Anti‐OX40 stimulation in vivo enhances CD8+ memory T cell survival and significantly increases recall responses

Abstract

There is growing evidence that engagement of OX40 (CD134), a member of the TNF receptor superfamily, can directly stimulate antigen-specific CD8⁺ T cells. It has been shown that CD8⁺ T cells express OX40 following activation, but the response of antigen-specific CD8⁺ T cells to OX40 stimulation has not been fully characterized. We utilized an antigen-specific transgenic CD8⁺ T cell model (OT-I) to determine if OX40 engagement can boost the generation of antigen-specific CD8⁺ T cell memory. Our results demonstrate that enhanced OX40 costimulation, via an agonist anti-OX40 antibody, increases CD25 and phospho-Akt expression on the antigen-specific CD8⁺ T cells and significantly increases the generation of long-lived antigen-specific CD8⁺ memory T cells. The increased numbers of memory CD8⁺ T cells generated via anti-OX40 treatment still required the presence of CD4⁺ T cells for their long-term maintenance in vivo. In addition, anti-OX40 costimulation greatly enhanced antigen-specific CD8⁺ T cell recall responses. These data show that OX40 engagement in vivo increases the number of antigen-specific CD8⁺ memory T cells surviving after antigen challenge and has implications for the development of more potent vaccines against pathogens and cancer.