EXTRATHYMIC CLONAL DELETION OF SELF-REACTIVE CELLS IN ATHYMIC MICE

The repertoire of T cells present in congenitally athymic mice was studied by flow cytometric analysis on populations of T cells expanded polyclonally in vitro. Athymic (BALB/c x C57BL/6)Fl mice have levels of potentially autoreactive V-beta-3- and V-beta-11-bearing T cells that are significantly higher than those of euthymic CB6F1 mice. Examination of potentially autoreactive cells in athymic AKR mice, however, yielded contrasting results. V-beta-6+ cells, which are deleted intrathymically in normal AKR mice, are present in the repertoire of young (< 6-wk-old) AKR nu/nu mice. Isolation of a cloned CD4+V-beta-6+ cell line with Mls-1a reactivity from young AKR nu/nu mice indicates that the correlation between TCR usage and specificity is consistent with that described in euthymic mice and that this population contains autoreactive T cells that are not anergic. By 6 mo of age, however, cells expressing V-beta-6 are no longer detectable. Inability to detect these cells is not simply caused by failure to expand these cells in culture, because freshly isolated populations from old nude mice exhibit the same selective absence of V-beta-6-bearing cells. The data strongly suggest that extrathymic deletion, rather than clonal anergy, accounts for the apparent absence of autoreactive V-beta-6-bearing cells in aged AKR nu/nu mice.