Age-associated decrease in virus-specific CD8+ T lymphocytes during primary influenza infection.
The mechanism of the age-associated decrease in CD8+ T cell response of mice to virus infection was examined in young adult (6 months) and aged (22 months) C57BL/6 mice during primary pulmonary influenza A virus infection. A significant age-associated decrease in both the percentage (P<0.0001) and number (P<0.05) of CD8+ T cells binding MHC Class I tetramers containing influenza A nucleoprotein (NP) epitope and in virus-specific CTL activity (P<0.05) was observed with pulmonary lymphocytes. The percentage of NP+CD8+ cells of individual mice strongly correlated with NP-specific cytotoxic activity (r(2)=0.77, P<0.02) and with the percentage of CD8+ cells that produced interferon-gamma (r(2)=0.86, P<0.002) in both young and aged mice. Comparable expression of the CD28, CD25, and the memory CD44(hi)/CD62L(lo) phenotype was detected on NP+CD8+ lymphocytes from mice of both age groups. There was a delay in the maximal expansion of NP+CD8+ cells in aged compared to young mice that paralleled a delay in maximal cytotoxic activity and in virus clearance. These data suggest that the age-related impairment of CD8+ lymphocyte activity during a primary influenza A infection is due to a defect in the expansion, rather than in effector activity, of influenza-specific CD8+ T cells.
Po
John Leander Z
JL
Department of Microbiology and Immunology, MCP Hahnemann School of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.
Gardner
Elizabeth M
EM
Anaraki
Farvardin
F
Katsikis
Peter D
PD
Murasko
Donna M
DM
D000375:Aging / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D007371:Interferon-gamma