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

Abstract

// Xin Zhou 1 , Jacob W. Hopkins 1 , Chongkai Wang 1 , Vinayak Brahmakshatriya 2 , Susan L. Swain 2 , George A. Kuchel 1 , Laura Haynes 1,* and Janet E. McElhaney 1,3 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 Abstract 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.