V-BETA GENE REPERTOIRES IN AGING MICE

To determine whether aging and thymic involution are associated with defects in intrathymic T cell selection or clonal instabilities, we compared transcript levels for 18 V(beta) genes in thymic and splenic T cells of young (2 month), adult (12 month), and old (20 month) mice of various Mls and MHC haplotypes (C57BL/6, BALB/c, and DBA/2). The results showed that the unselected thymic V(beta) repertoires remain stable throughout life, despite severe reduction in cellularity in the thymus of aged mice. Similarly, splenic CD4 and CD8 V(beta) repertoires showed no significant alterations, and no leakage to the periphery of endogenous superantigen-reactive V(beta) clones was observed with age, even in irradiated and bone marrow-reconstituted old mice. Responses in vitro to bacterial superantigens were undiminished with age but, significantly, some of these superantigens expanded V(beta) clones that are cross-reactive with endogenous superantigens and are normally partially (V(beta)11 and -12) or severely (V(beta)3.1) deleted in BALB/c mice. In the course of these studies, several previously unrecognized reactivities of V(beta) with staphylococcal toxins were also revealed.