UMMS Affiliation

Department of Pathology

Date

6-14-2016

Document Type

Article

Disciplines

Immunology of Infectious Disease | Immunopathology | Virus Diseases

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.

Rights and Permissions

Citation: Oncotarget. 7(26), 39171-39183. 2016 Jun 14. doi: 10.18632/oncotarget.10047. Link to article on publisher's site

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.

DOI of Published Version

10.18632/oncotarget.10047

Related Resources

Link to Article in PubMed

Keywords

CD8 T cell, Gerotarget, aging, granzyme B, influenza, interleukin-2, interleukin-6, perforin

Journal Title

Oncotarget

PubMed ID

27322555

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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