NONEXCLUSIVE FAS CONTROL AND AGE-DEPENDENCE OF VIRAL SUPERANTIGEN-INDUCED CLONAL DELETION IN LUPUS-PRONE MICE

To investigate the role of Fas in the induction of tolerance by viral superantigen (SAG), we infected MRL-+/+ and MRL-1pr (Fas mutant) mice with mouse mammary tumor virus (MMTV) (SW), a virus encoding an SAG wi th the same specificity as endogenous Mtv-7-SAG. In normal mice, this infection has two distinct consequences on specific V beta 6(+)CD4(+) T cells, consisting of activation followed by clonal deletion. MMTV (S W)-SAG-induced activation in vivo was identical in MRL-+/+ and MRL-1pr mice. In contrast, clonal deletion showed age-dependent impairment. E arly infection (5 weeks) led to identical clonal deletion of specific T cells in blood lymphocytes from MRL-+/+ and MRL-1pr mice, although c lonal deletion was slightly impaired in the MRL-lpr lymph nodes. Late infection (10 weeks) of MRL-lpr mice led to markedly delayed and reduc ed clonal deletion. V beta 6(+)CD4(+) T cells which escaped clonal del etion in aging MRL-lpr mice were not anergized by interaction with SAG . These results show that peripheral clonal deletion induced by viral SAG in adult mice is controlled by Fas, but not exclusively so.