Transplantation of metanephroi across the major histocompatibility complex in rats

Abstract

To determine whether transplanted metanephroi grow, differentiate, and function in hosts that differ in major histocompatibility complex loci (RT1 loci in rats) from donors in a defined way, we implanted metanephroi from embryonic day( E) 15 PVG (RT1c) rat embryos into the omentum of nonimmunosupressed uninephrectomized PVG-RT1avl (host) rats. By 4 wk posttransplantation, metanephroi had grown and differentiated such that glomeruli, proximal and distal tubules, and collecting ducts had normal structure and ultrastructure. At 12 wk posttransplantation, weights of metanephroi were 54 ± 8 mg. Inulin clearances were 0.9 ± 0.3 μl · min−1 · 100 g rat wt−1. In vitro, splenocytes from PVG rats stimulated the proliferation of cells originating from both PVG-RT1avlrats in which a transplant had been performed and PVG-RT1avl rats with no transplant. Full-thickness PVG-RT1avl skin engrafted normally on PVG-RT1avl rats in which PVG metanephroi had been previously implanted and metanephroi retained a normal appearance. In contrast, skin from PVG rats sloughed, and the tubular architecture of metanephroi was obliterated by a mononuclear cell infiltrate consistent with acute rejection. Here we show for the first time that functional chimeric kidneys develop from metanephroi transplanted across the MHC into nonimmunosupressed hosts and provide evidence that a state of peripheral immune tolerance secondary to T cell “ignorance” permits their survival.