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

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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.