Fas on renal parenchymal cells does not promote autoimmune nephritis in MRL mice

Background. Although Fas on pancreatic islets promotes autoimmune diabetes in mice, the role of Fns expression on kidney parenchymal cells during auto immune disease is unknown. Methods. To determine whether Fas on renal parenchymal cells promotes autoi mmune renal destruction, we compared apoptosis and pathology in Fas-intact and Fas-deficient kidneys in an autoimmune milieu. For this purpose, we tra nsplanted single, normal kidneys from MRL-++ (Fns-intact) mice (3 months of age) into age-matched, congenic MRL-Fas(lpr) (Fas-deficient) recipients af ter removal of nephritic kidneys. These Fas-intact kidneys were compared wi th Fas-deficient nephritic kidneys. Results. There is a progressive increase of FasL on kidney infiltrating cel ls and Fns and Fast on renal parenchymal cells in MRL-++ kidneys during eng raftment (0, 2, 4-6, and 8 weeks). By comparison, we detected an increase i n Fast in MRL-Fas(lpr) kidneys (3 to 5 months of age), whereas Fas was not detectable. The engagement of T cells bearing Fast with Fas expressing tubu lar epithelial cells (TECs) induced TEC apoptosis ill vitro. However, apopt osis and pathology were similar in kidneys (MRL-++, 8 weeks postengraftment vs. MRL-Fas(lpr), 5 months) with equivalent amounts of FasL-infiltrating c ells or FasL TECs, regardless of Fas on renal parenchymal cells. Conclusion. The expression of Fas on renal parenchymal cells does not incre ase apoptosis or promote renal disease in MRL-++ mice. We speculate that th e autoimmune milieu evokes mechanisms that mask, counter, or pre-empt Fas-F asL-initiated apoptosis in MRL kidneys.