title: An alternative signal 3: CD8⁺ T cell memory independent of IL-12 and type I IFN is dependent on CD27/OX40 signaling.
abstract: Type I IFN and IL-12 are well documented to serve as so called "signal 3" cytokines, capable of facilitating CD8(+) T cell proliferation, effector function and memory formation. While their ability to serve in this capacity is well established, to date, no non-cytokine signal 3 mediators have been clearly identified. We have established a vaccine model system in which the primary CD8(+) T cell response is independent of either IL-12 or type I IFN receptors, but dependent on CD27/CD70 interactions. We show here that primary and secondary CD8(+) T cell responses are generated in the combined deficiency of IFN and IL-12 signaling. In contrast, antigen specific CD8(+) T cell responses are compromised in the absence of the TNF receptors CD27 and OX40. These data indicate that CD27/OX40 can serve the central function as signal 3 mediators, independent of IFN or IL-12, for the generation of CD8(+) T cell immune memory.
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver, National Jewish Health, CO 80206, United States. phillip-sanchez@uiowa.edu
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Sanchez
authors.forename: Ross M
authors.initials: RM
authors.lastname: Kedl
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D007370:Interferon Type I / Q000172:deficiency / Q000276:immunology*; D018664:Interleukin-12 / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053262:Receptors, OX40 / Q000378:metabolism*; D015398:Signal Transduction; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D018664:Interleukin-12