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.
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.
UConn Center on Aging and Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA.
Xin
X
Zhou
UConn Center on Aging and Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA.
Jacob W
JW
Hopkins
UConn Center on Aging and Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA.
Chongkai
C
Wang
Department of Pathology, University of Massachusetts Medical School, North Worcester, MA, USA.
Vinayak
V
Brahmakshatriya
Department of Pathology, University of Massachusetts Medical School, North Worcester, MA, USA.
Susan L
SL
Swain
UConn Center on Aging and Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA.
George A
GA
Kuchel
UConn Center on Aging and Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA.
Laura
L
Haynes
UConn Center on Aging and Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA.|Health Sciences North Research Institute, Sudbury, ON, Canada.
Janet E
JE
McElhaney
D000375:Aging; D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D049109:Cell Proliferation; D053804:Granzymes / Q000737:chemistry; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype; D007252:Influenza Vaccines; D007251:Influenza, Human / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology
C508594:IL2 protein, human; C508600:IL6 protein, human; D007252:Influenza Vaccines; D007376:Interleukin-2; D015850:Interleukin-6; C577686:interleukin-6, mouse; D053804:Granzymes
CD8 T cell; Gerotarget; aging; granzyme B; interleukin-2; interleukin-6