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 with 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 (SW)-SAG-induced activation in vivo was identical in MRL-+/+ and MRL-1pr mice. In contrast, clonal deletion showed age-dependent impairment. Early infection (5 weeks) led to identical clonal deletion of specific T cells in blood lymphocytes from MRL-+/+ and MRL-1pr mice, although clonal deletion was slightly impaired in the MRL-lpr lymph nodes. Late infection (10 weeks) of MRL-lpr mice led to markedly delayed and reduced clonal deletion. V beta 6(+)CD4(+) T cells which escaped clonal deletion 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.