Lower GrB+ CD62Lhigh CD8 TCM effector lymphocyte response to influenza virus in older adults is associated with increased CD28null CD8 T lymphocytes

Older adults who are at risk of developing influenza illness, have a low level of influenza virus-stimulated cytotoxic T lymphocyte (CTL) activity as measured by an assay of granzyme B (GrB). The purpose of this study was to determine whether aging affected memory CTL populations identified by GrB expression in influenza virus-stimulated peripheral blood mononuclear cells (PBMC). The expression and activity of GrB increased with virus stimulation over 5 days of culture. Virus-specific CD8 effector T cells with the phenotype, GrB+ CD62Lhigh CD8 TCM, were found to be the source of the early CTL response to influenza virus. Comparing the CD8 T cell response in 5-day PBMC cultures of 161 adult subjects, the response of GrB+ CD62Lhigh CD8 TCM lymphocytes in older individuals was significantly lower than in younger adults after viral stimulation (p < 0.001). The increase in the proportion of CD28null CD8 T cells in fresh PBMC negatively correlated with the proportion GrB+ CD62Lhigh CD8 TCM lymphocytes in virus-stimulated PBMC. Thus, the increase in CD28null CD8 T cells with age may contribute to the limited CTL response to influenza vaccination and diminished protection in older adults.