TRANSGENIC TUBULAR CELL EXPRESSION OF CLASS-II IS INSUFFICIENT TO INITIATE IMMUNE RENAL INJURY

Autoimmune disease in mouse models of lupus nephritis is associated wi th enhanced renal tubular epithelial cell (TEC) expression of major hi stocompatibility complex (MHC) class II (Ia) molecules. It is unknown whether de novo TEC expression of syngeneic la alone can initiate immu ne attack or whether expression is secondary to cytokines released by infiltrating lymphocytes. To establish if the expression of high level s of self-MHC molecules alone can initiate immune renal injury in the adult animal, kidneys from transgenic C57BL/6 (B6) mice (Ins-I-E) bear ing constitutively high levels of I-E(b) on proximal TEC were transpla nted into nephrectomized male B6 x C3H Fl hybrid mice (I-E(b/k)). Cont rol mice received kidneys from I-E(b) negative, nontransgenic B6 mice, and all transplant recipient mice were evaluated for renal disease. A t the end of the study (>8.3 months mean survival), the transgenic tra nsplant recipients did not become proteinuric (<l+ urinary protein) an d had normal serum creatinine levels (control = 95 +/- 8 versus transg enic transplants = 116 +/- 2 3 mumol/L; N = four/group), and the kidne ys remained histologically normal. These results establish that the ex pression of high levels of transgenic MHC class II molecules on TEC is insufficient to initiate autoimmune injury in this model. It is sugge sted that, in addition to MHC class II molecules, other signals or acc essory molecules are required from TEC to initiate immune renal injury .