Department of Pathology
Immunology of Infectious Disease | Immunopathology | Virus Diseases
An age-related decline in cytolytic activity has been described in CD8+ T cells and we have previously shown that the poor CD8+ effector T cell responses to influenza A/H3N2 challenge result from a decline in the proportion and function of these cytolytic T lymphocytes (CTL). Here, we describe that addition of exogenous cytokines to influenza-stimulated PBMC from both aged mice and humans, enhances the generation of influenza specific CD8 CTL by increasing their proliferation and survival. Our data show that the addition of IL-2 and IL-6 to splenocytes from mice previously infected with influenza virus restores the aged CD8+ T cell response to that observed in young mice. In humans, IL-2 plus IL-6 also reduces the proportion of apoptotic effector CD8+ T cells to levels resembling those of younger adults. In HLA-A2+ donors, MHC Class I tetramer staining showed that adding both exogenous IL-2 and IL-6 resulted in greater differentiation into influenza-specific effector CD8+ T cells. Since this effect of IL-2/IL-6 supplementation can be reproduced with the addition of Toll-like receptor agonists, it may be possible to exploit this mechanism and design new vaccines to improve the CD8 T cell response to influenza vaccination in older adults.
CD8 T cell, Gerotarget, aging, granzyme B, influenza, interleukin-2, interleukin-6, perforin
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DOI of Published Version
Oncotarget. 7(26), 39171-39183. 2016 Jun 14. doi: 10.18632/oncotarget.10047. Link to article on publisher's site
Zhou, Xin; Hopkins, Jacob W.; Wang, Chongkai; Brahmakshatriya, Vinayak; Swain, Susan L.; Kuchel, George A.; Haynes, Laura; and McElhaney, Janet E., "IL-2 and IL-6 cooperate to enhance the generation of influenza-specific CD8 T cells responding to live influenza virus in aged mice and humans" (2016). Open Access Articles. 2809.
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This work is licensed under a Creative Commons Attribution 3.0 License.