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Vaccine. 2012 Feb 1;30(6):1154-61. doi: 10.1016/j.vaccine.2011.12.017. Epub 2011 Dec 14.

An alternative signal 3: CD8⁺ T cell memory independent of IL-12 and type I IFN is dependent on CD27/OX40 signaling.

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Integrated Department of Immunology, University of Colorado Denver, National Jewish Health, CO 80206, United States.


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.

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