Virus-specific T cell clonal expansions can limit recall responses to secondary respiratory virus infections (104.4)

Abstract

Abstract Respiratory virus infections are a major health problem in the elderly. This is due to declining immune responsiveness in the elderly and the development of CD8+ T cell clonal expansions (TCE) that perturb the memory T cell pool. We recently showed that TCE can arise over time from memory CD8+ T cells established by an acute respiratory viral infection. Virus-specific TCE are phenotypically identical to conventional memory cells and do not express the characteristics of exhausted cells. Since TCE can dominate the memory T cell pool, it is essential to determine the rate at which they develop, and their ability to mount a recall response to secondary pathogen challenge in vivo. In the current study, we developed an assay to detect developing TCE in a cohort of mice following Sendai virus infection and found a progressive increase in the appearance of TCE within the first year following infection. Using a dual adoptive transfer approach to address the recall potential of virus-specific TCE, we demonstrate that the majority of TCE examined are poorly responsive to a secondary infection. Taken together, the data suggest that the development of TCE is a common occurrence due to the progressive dysregulation of the virus-specific memory T cell pool with age, and many TCE are profoundly defective in their ability to mediate recall responses.