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George M. O'Brien Kidney and Urological Disease Center, Renal Division, Departments of Medicine, Cell Biology and Physiology, and Pathology, Washington University School of Medicine, St. Louis, Missouri 63110
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
wt1. In vitro, splenocytes from PVG rats stimulated the
proliferation of cells originating from both PVG-RT1avl
rats 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.
development; glomerular filtration; immune tolerance; kidney; T cell ignorance
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  M. R. Dilworth, M. J. Clancy, D. Marshall, C. A. Bravery, P. E. Brenchley, and N. Ashton Development and functional capacity of transplanted rat metanephroi Nephrol. Dial. Transplant., March 1, 2008; 23(3): 871 - 879. [Abstract] [Full Text] [PDF]
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