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

Authors

  • Carl E. Ruby,

    1. Laboratory of Basic Immunology, Earle A. Chiles Research Institute, Robert W. Franz Research Center, Providence Portland Medical Center, Portland, OR
    2. Oregon Health and Science University, Portland, OR
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  • William L. Redmond,

    1. Laboratory of Basic Immunology, Earle A. Chiles Research Institute, Robert W. Franz Research Center, Providence Portland Medical Center, Portland, OR
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  • Daniel Haley,

    1. Immunological Monitoring Laboratory, Earle A. Chiles Research Institute, Robert W. Franz Research Center, Providence Portland Medical Center, Portland, OR
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  • Andrew D. Weinberg

    Corresponding author
    1. Laboratory of Basic Immunology, Earle A. Chiles Research Institute, Robert W. Franz Research Center, Providence Portland Medical Center, Portland, OR
    2. Oregon Health and Science University, Portland, OR
    • Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, 4805 N.E. Glisan, Portland, OR 97213, USA, Fax: +1-503-215-6841
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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.

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