The expansion of a CD4+ T cell population bearing a distinctive β chain in MRL lpr/lpr mice suggests a role for the fas protein in peripheral T cell selection

Abstract

MRL lpr/lpr mice suffer from a systemic lupus erythematosus-like autoimmune disease. The lpr mutation impairs the normal transcription of the fas message, the product of which mediates apoptosis and presumably the proper selection of T cells. We have found an early expansion of CD4⁺ T cells bearing a distinctive Vβ8.3-Dβ1.1-Jβ1.1 T cell receptor β chain in the periphery of MRL lpr/lpr mice, which was not detected in MRL +/+ mice nor in the thymus of MRL lpr/lpr mice. Thus, since thymic selection is normal in MRL lpr/lpr mice, we propose that the lpr mutation results in defective negative selection at the periphery.