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

Abstract

Abstract 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.

Keywords

• T cell receptor repertoire
• Acute respiratory virus infection
• CD8⁺ T cell memory maintenance
• T cell clonal expansion