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

Eur J Immunol. 2007 Jan;37(1):157-66. doi: 10.1002/eji.200636428.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies / administration & dosage*
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cell Survival / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Immunologic Memory*
  • Immunophenotyping
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, OX40 / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / transplantation


  • Antibodies
  • Epitopes, T-Lymphocyte
  • Receptors, OX40
  • Tnfrsf4 protein, mouse