Early dysregulation of the memory CD8(+) T cell repertoire leads to compromised immune responses to secondary viral infection in the aged

BACKGROUND: Virus-specific memory CD8(+) T cells persist long after infection is resolved and are important for mediating recall responses to secondary infection. Although the number of memory T cells remains relatively constant over time, little is known about the overall stability of the memory T cell pool, particularly with respect to T cell clonal diversity. In this study we developed a novel assay to measure the composition of the memory T cell pool in large cohorts of mice over time following respiratory virus infection. RESULTS: We find that the clonal composition of the virus-specific memory CD8(+) T cell pool begins to change within months of the initial infection. These early clonal perturbations eventually result in large clonal expansions that have been associated with ageing. CONCLUSIONS: Maintenance of clonal diversity is important for effective long-term memory responses and dysregulation of the memory response begins early after infection.