Fas ligand expression and function in systemic lupus erythematosus.
Mutations in the Fas receptor or its ligand (FasL) lead to lupus-like systemic autoimmune diseases in mice and in some humans. To determine whether a significant number of patients with systemic lupus erythematosus (SLE) have impaired FasL function, we compared T cell effector function by superantigen-activated CD4+ T cell lines or by anti-CD3- and IL-2-generated cytotoxic T cells. No differences were observed between SLE and normal control superantigen-derived CD4+ T cells in either the ability of these cells to up-regulate Fas expression or to induce apoptosis of the Fas-sensitive target B cells. When anti-CD3/IL-2-activated T cells were examined, SLE T cells had a modest reduction (-8%) in T cell cytotoxicity compared with normal controls, but the reduction was similar to the rheumatoid arthritis disease controls. A modest reduction in cytotoxicity was evident in both the Fas and perforin/granzyme pathways as determined by testing Fas-positive and -negative targets as well as by selective blockade of the perforin/granzyme pathway with concanamycin. These results indicate that no specific defects in FasL function are evident in the majority of SLE patients under the in vitro conditions tested. The proportional reduction in FasL and perforin/granzyme function in SLE and rheumatoid arthritis patients following anti-CD3/IL-2 stimulation most likely reflects subtle differences in activation in patient-derived vs normal control T cells.
McNally
J
J
Hospital for Special Surgery, Cornell University Medical Center, New York, NY 10021, USA.
Yoo
D H
DH
Drappa
J
J
Chu
J L
JL
Yagita
H
H
Friedman
S M
SM
Elkon
K B
KB
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D053222:Fas Ligand Protein; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins