MATURE CD4-LYMPHOCYTES FROM MRL( T)LPR MICE ARE RESISTANT TO RECEPTOR-MEDIATED TOLERANCE AND APOPTOSIS/

The goal of this study was to examine the functional responses and tol erance susceptibility of T lymphocytes from mice of the autoimmune str ain, MRL/lpr. A population of autoreactive CD4+ T cells can be readily expanded from the lymphoid tissues of young lpr mice. Lines of IL-2-p roducing autoreactive and alloreactive lpr and alloreactive +/+ T cell s were developed to study their responses to tolerance-inducing stimul i. Culture of +/+ T cells with high concentrations of immobilized anti -CD3 antibody induces both functional anergy and apoptosis. By contras t, lpr-derived T cell lines are relatively resistant to anergy and apo ptosis. The implications of these findings for the development of auto immunity, and the possible role of the Fas Ag in determining resistanc e or susceptibility to tolerance, are discussed.