Increased expression of functional Fas-ligand in activated T cells from patients with systemic lupus erythematosus.
The Fas ligand induces apoptosis upon binding to Fas/APO-1 (CD95) bearing target cells. Activation induced cell death (AICD) in T cells is mediated by upregulation of Fas ligand on the cell surface membrane upon crosslinking of the TCR. AICD is considered to be essential for the elimination of autoreactive T cells in the peripheral blood. To elucidate possible abnormalities in the process of AICD in human SLE, we studied the expression and function of Fas ligand in polyclonal T cell lines from patients with SLE, patients with other rheumatic diseases and normal controls. SLE T cells expressed on their surface significantly higher amounts of Fas ligand compared to the two control groups. Stimulation of the cells with anti-CD3 mAb lead to further increase in surface membrane Fas ligand expression in all three groups with SLE expressing the highest amounts. The percentage of increase was though lower in SLE T cells than in normal T cells or disease control cells. The T cells were examined for Fas ligand-mediated cytotoxicity in a 51Cr release assay using Fas-expressing normal T cells as target cells. There was no difference in SLE and control T cells with regard to specific 51Cr lysis, indicating that the Fas ligand expressed by the SLE T cells is functional. Our data show that activated T cells from patients with SLE express high amounts of functional Fas ligand with intact TCR-mediated upregulation. This could account for the high apoptotic rates that have been observed in lymphocytes from patients with SLE.
Kovacs
B
B
Department of Clinical Physiology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Liossis
S N
SN
Dennis
G J
GJ
Tsokos
G C
GC
D000328:Adult; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002453:Cell Cycle; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell