title: 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.
authors.affiliation: Laboratory of Basic Immunology, Earle A. Chiles Research Institute, Robert W. Franz Research Center, Providence Portland Medical Center, Portland, OR 97213, USA.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Ruby
authors.forename: William L
authors.initials: WL
authors.lastname: Redmond
authors.forename: Daniel
authors.initials: D
authors.lastname: Haley
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Weinberg
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053262:Receptors, OX40 / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation
chemical_list: D000906:Antibodies; D018984:Epitopes, T-Lymphocyte; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse