Apoptosis and reduced influenza A virus specific CD8+ T cells in aging mice.
Some studies have reported increased apoptosis in CD8(+) T cells from aged mice. We previously demonstrated diminished virus-specific CD8(+) cytotoxic T lymphocyte (CTL) activity in aged mice in comparison to young mice. The present study investigated the role of apoptosis in age-related influenza virus-specific CD8(+) CTL deficiency. Splenocytes from influenza-primed aged and young mice were stimulated in vitro with virus. The CD8(+) T cell/total lymphocyte ratios correlated with CTL activity and were significantly decreased and increased in aged and young mice, respectively. Fas, FasL, TNF-alpha and TNFR-p55 expression, measured by flow cytometry, ELISA and/or RT-PCR, were significantly elevated in aged mice. Apoptotic CD8(+) T cells (Annexin V binding) were also elevated in aged mice. IL-12 treatment increased CD8(+) CTL activity and IFN-gamma production but did not affect apoptosis. Thus, apoptosis may contribute to reduced influenza virus-specific CD8(+) T cell frequency, CTL deficiency and increased influenza disease in aging.
Zhang
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Y
Influenza Research Center, Respiratory Pathogens Research Unit, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, TX 77030, USA.
Wang
Y
Y
Gilmore
X
X
Xu
K
K
Chen
M
M
Tebebi
P
P
Mbawuike
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IN
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000375:Aging / Q000276:immunology* / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D053222:Fas Ligand Protein; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
D000276:Adjuvants, Immunologic; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor; D018664:Interleukin-12; D007371:Interferon-gamma