Age-related dysregulation in CD8 T cell homeostasis: Kinetics of a diversity loss

Relative diversity and representation of peripheral T cells bearing differe nt TCR V beta families are remarkably tightly regulated between birth and a dvanced adulthood. By contrast, individual elderly humans and C3H.SW and B1 0.BR aged mice display drastic disruption in such regulation. It was sugges ted that the alterations in the murine aged T cell compartment were due to age-related clonal T cell expansions (TCE), Here, we studied the kinetics o f homeostatic dysregulation of T cell populations in aged C57BL/6 (B6) mice . Using mAb staining, we show that the percentages of alpha beta (+)CD8(+) or CD4(+) T cells bearing different TCRV beta elements remain virtually con stant in mice up to 12 mo of age. In 22-mo-old mice, however, there is a dr amatic disturbance of this pattern owing to the emergence of CD8(+) TCE, Ex panded T cells did not show any obvious bias in VP usage and were derived i n all cases examined thus far from a single clone, TCE appeared later in li fe, compared with B cell clonal expansions. However, and in contrast to tho se detected in humans, TCE were frequently unstable disappearing within 2-4 mo, with other TCE appearing within the same time frame. Additional studie s carried on thymic T cells, thymectomized mice, acid young T transferred c ells into Rag1(-/-) mice suggest that the clonal expansions occur in the pe riphery and that their onset is accelerated by decreased thymic output and/ or function(s).