FAS LIGAND EXPRESSION AND FUNCTION SYSTEMIC LUPUS-ERYTHEMATOSUS

Mutations in the Fas receptor of its ligand (Fast) lead to lupus-like systemic autoimmune diseases in mice and in some humans, To determine whether a significant number of patients with systemic lupus erythemat osus (SLE) have impaired East function, we compared T cell effector fu nction by superantigen-activated CD4(+) T cell lines or by anti-CD3- a nd IL-2-generated cytotoxic T cells, No differences were observed betw een SLE and normal control superantigen-derived CD4(+) T cells in eith er the ability of these cells to up-regulate Fas expression or to indu ce apoptosis of the Fas-sensitive target B cells, When anti-CD3/IL-2-a ctivated T cells were examined. SLE T cells had a modest reduction (-8 %) in T cell cytotoxicity compared with normal controls, but the reduc tion was similar to the rheumatoid arthritis disease controls, A modes t reduction in cytotoxicity was evident in both the Fas and perform/gr anzyme pathways as determined by testing Fas-positive and -negative ta rgets as well as by selective blockade of the perform/granzyme pathway with concanamycin. These results indicate that no specific defects in Fast function are evident in the majority of SLE patients under the i n vitro conditions tested. The proportional reduction in Fast and perf orm/granzyme function in SLE and rheumatoid arthritis patients followi ng anti-CD3/IL-2 stimulation most likely reflects subtle differences I n activation in patient-derived vs normal control T cells.