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

Fas on renal parenchymal cells does not promote autoimmune nephritis in MRL mice. Although Fas on pancreatic islets promotes autoimmune diabetes in mice, the role of Fas expression on kidney parenchymal cells during autoimmune disease is unknown. To determine whether Fas on renal parenchymal cells promotes autoimmune renal destruction, we compared apoptosis and pathology in Fas -intact and Fas -deficient kidneys in an autoimmune milieu. For this purpose, we transplanted single, normal kidneys from MRL-++ ( Fas -intact) mice (3 months of age) into age-matched, congenic MRL- Fas lpr ( Fas -deficient) recipients after removal of nephritic kidneys. These Fas -intact kidneys were compared with Fas -deficient nephritic kidneys. There is a progressive increase of Fas L on kidney-infiltrating cells and Fas and Fas L on renal parenchymal cells in MRL-++ kidneys during engraftment (0, 2, 4–6, and 8 weeks). By comparison, we detected an increase in Fas L in MRL- Fas lpr kidneys (3 to 5 months of age), whereas Fas was not detectable. The engagement of T cells bearing Fas L with Fas expressing tubular epithelial cells (TECs) induced TEC apoptosis in vitro. However, apoptosis and pathology were similar in kidneys (MRL-++, 8 weeks postengraftment vs. MRL- Fas lpr, 5 months) with equivalent amounts of Fas L-infiltrating cells or Fas L TECs, regardless of Fas on renal parenchymal cells. The expression of Fas on renal parenchymal cells does not increase apoptosis or promote renal disease in MRL-++ mice. We speculate that the autoimmune milieu evokes mechanisms that mask, counter, or pre-empt Fas-Fas L-initiated apoptosis in MRL kidneys.