title: OX40 drives protective vaccinia virus-specific CD8 T cells.
abstract: Vaccinia virus (VACV) affords long-lasting protection against variola virus, the agent of smallpox. VACV-reactive CD8 T cells contribute to protection but their molecular control is unknown. We show that the TNFR molecule OX40 (CD134) controls primary VACV-specific CD8 T cell expansion and antiviral cytokine production and dictates development of strong memory to both dominant and subdominant VACV epitopes. Using adoptive transfer of OX40-deficient CD8 TCR-transgenic T cells responding to Ag in the context of VACV infection, we found that this reflects a direct action of OX40 expressed by CD8 T cells. Furthermore, CD8 T cells that can protect against lethal VACV challenge do not develop in mice deficient in OX40. Thus, OX40, which has been found to play little if any role in the generation of CD8 T cells to several viruses, including lymphocytic choriomeningitis virus and influenza, plays a dominant role in shaping the CD8 T cell response to VACV. These data suggest that unique costimulatory pathways might control alternate antiviral CD8 responses, demonstrating the plasticity of the immune response in utilizing different mechanisms to achieve similar ultimate goals.
authors.affiliation: Division of Molecular Immunology, La JollaInstitute for Allergy and Immunology, San Diego, CA 92037, USA.
authors.forename: Shahram
authors.initials: S
authors.lastname: Salek-Ardakani
authors.forename: Magdalini
authors.initials: M
authors.lastname: Moutaftsi
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D016207:Cytokines / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D053262:Receptors, OX40 / Q000235:genetics / Q000276:immunology*; D012899:Smallpox / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D014616:Vaccinia virus / Q000276:immunology*; D012901:Variola virus / Q000276:immunology
chemical_list: D016207:Cytokines; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse