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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.