title: Aging and lymphocyte function: a model for testing gerontologic hypotheses of aging in man.
abstract: Advanced age in humans and experimental animal models has been consistently associated with declines in the in vivo and in vitro responsiveness of T lymphocytes. The declines in vitro responses cannot be explained by decrease in numbers of differentiated T cells or by age-associated changes in the proportion of CD4+ 'helper' to CD8+ 'cytotoxic/suppressor' T cells. However, recent studies have demonstrated a decline with age in numbers of what appear to be antigenically 'naive' or 'virgin' T cells, accompanied by a proportionate increase in 'memory' T cells which mediate anemnestic or recall responses to previously encountered antigens. The findings lead to the hypothesis that thymic involution leads to decline in input of newly differentiated 'naive' T cells, while T cell number in peripheral tissues is maintained by accumulation of longer lived 'memory' T cells due to lifetime antigen exposure. So far, limited data suggest that increasing average biological age of the memory T cells which accumulate with age is largely responsible for declines in vitro activation responses of human peripheral blood T cells and that a subset of these memory T cells becomes refractory to activation stimuli as a consequence of in vivo cellular aging. Approaches to testing this hypothesis are presented and the implications of these findings for use of memory T cells as a model for investigating the mechanisms of in vivo cellular aging, are discussed.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, U.S.A.
authors.forename: J J
authors.initials: JJ
authors.lastname: O'Leary
authors.forename: H M
authors.initials: HM
authors.lastname: Hallgren