Age-associated decreases in influenza-specific CD8+ T cell immunity and the effect of androgen removal (B18)

Abstract

Abstract Age-associated decreases in the CD8+ T cell primary and secondary responses of mice to influenza A virus infection were examined by comparing young (2 months) and aged (22–24 months) C57BL/6 mice. A significant age-associated decrease was seen in both the percentage and number of virus-specific CD8+ T cells following both primary and secondary infection. In both age groups there was a strong correlation between influenza peptide-specific tetramer+ and IFNg+ cells. Clearance of virus from the lungs, following primary infection corresponded with the time point at which maximal levels of both percentages and numbers of virus-specific CD8+ T cells were seen for both age groups. There was a delay in the maximal expansion of virus-specific CD8+ T cells in the aged mice compared to young mice following primary infection and a corresponding delay in viral clearance. A significant age-associated decrease in the cytotoxic activity was seen. Cytotoxic activity was closely correlated with the numbers of virus-specific CD8+ T cells suggesting that the age-associated problems with CD8+ T cell activity against influenza are due to decreased numbers of cells able to respond initially or a defect in expansion of these cells once exposed to the virus, rather than effector activity on a per cell basis. This was further supported by the fact that following thymic regeneration, caused by castration, there was an increase in the numbers of naïve T cells in the periphery of aged-mice with a consequent increase in the numbers of virus-specific cells and an increased ability to clear virus.