Figure 4.

Decreasing regenerative reserve in immunosenescence. Hypothesis: In the elderly, dysfunctional, often CD8+ CMV- specific T cells accumulate because apoptotic pathways are compromised. Vital memory cells are eventually lost by clonal attrition (clonal exhaustion). Loss of memory cells for previously encountered pathogens contributes to morbidity and mortality. Thus, decreased clonal heterogeneity correlates with mortality in longitudinal studies. Because T cell homeostasis maintains constant numbers of T cells in the periphery, even the age-associated decreased thymic-output of naive cells is blocked, and the shrinkage of the naive T cell repertoire contributes to increased susceptibility to newly-encountered infectious diseases. IM, infectious mononucleosis; PD, population doublings.