Research Papers: Gerotarget (Focus on Aging):

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

Xin Zhou _, Jacob W. Hopkins, Chongkai Wang, Vinayak Brahmakshatriya, Susan L. Swain, George A. Kuchel, Laura Haynes and Janet E. McElhaney

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Oncotarget. 2016; 7:39171-39183. https://doi.org/10.18632/oncotarget.10047

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Xin Zhou1, Jacob W. Hopkins1, Chongkai Wang1, Vinayak Brahmakshatriya2, Susan L. Swain2, George A. Kuchel1, Laura Haynes1,* and Janet E. McElhaney1,3

1 UConn Center on Aging and Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA

2 Department of Pathology, University of Massachusetts Medical School, North Worcester, MA, USA

3 Health Sciences North Research Institute, Sudbury, ON, Canada

* Denotes co-senior author

Correspondence to:

Janet E. McElhaney, email:

Keywords: aging, CD8 T cell, interleukin-2, interleukin-6, granzyme B, Gerotarget

Received: April 02, 2016 Accepted: June 01, 2016 Published: June 14, 2016


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.

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