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
Authors
Zhou, XinHopkins, Jacob W.
Wang, Chongkai
Brahmakshatriya, Vinayak
Swain, Susan L.
Kuchel, George A.
Haynes, Laura
McElhaney, Janet E.
UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2016-06-14Keywords
CD8 T cellGerotarget
aging
granzyme B
influenza
interleukin-2
interleukin-6
perforin
Immunology of Infectious Disease
Immunopathology
Virus Diseases
Metadata
Show full item recordAbstract
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.Source
Oncotarget. 7(26), 39171-39183. 2016 Jun 14. doi: 10.18632/oncotarget.10047. Link to article on publisher's site
DOI
10.18632/oncotarget.10047Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40000PubMed ID
27322555Related Resources
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10.18632/oncotarget.10047
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