REPAIR MECHANISM OF LUPUS NEPHRITIS IN (NZBXNZW)F-1 MICE BY ALLOGENEIC BONE-MARROW TRANSPLANTATION

We have recently found that allogeneic bone marrow transplantation (BM T) can be used to treat lupus nephritis in (NZB x NZW)F-1(B/WF1), BXSB , MRL/lpr and (NZW x BXSB)F-1 mice. To elucidate why and how glomerula r damage is repaired by BMT, serial renal biopsies were carried out us ing B/WF1 mice before and after BMT. Donor-derived B cells and macroph ages with normal functions developed two weeks (wks) after BMT. At thi s stage, the macrophages did not show immune complex (IC) clearance ac tivity. Donor-derived T cells with normal functions were generated six wks after BMT. At this stage, visceral epithelial cells, macrophages and mesangial cells in the glomeruli were activated by T cells and sho wed marked phagocytic activity: macrophages and mesangial cells were f ound to be responsible for the clearance of ICs, whereas, to our surpr ise, epithelial cells were found to be responsible for the repair of i njured basement membranes. These findings suggest that T cells with no rmal functions, which have the capacity to activate macrophages, mesan gial cells and epithelial cells, play a crucial role in repairing IC-m ediated glomerular damage.