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
Hopkins, Jacob W.
Swain, Susan L.
Kuchel, George A.
McElhaney, Janet E.
UMass Chan AffiliationsDepartment of Pathology
Document TypeJournal Article
KeywordsCD8 T cell
Immunology of Infectious Disease
MetadataShow full item record
AbstractAn 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.
Oncotarget. 7(26), 39171-39183. 2016 Jun 14. doi: 10.18632/oncotarget.10047. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40000
RightsAll site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
Except where otherwise noted, this item's license is described as All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.