Repair mechanism of lupus nephritis in (NZB x NZW)F1 mice by allogeneic bone marrow transplantation.

We have recently found that allogeneic bone marrow transplantation (BMT) can be used to treat lupus nephritis in (NZB x NZW)F1(B/WF1), BXSB, MRL/lpr and (NZW x BXSB)F1 mice. To elucidate why and how glomerular damage is repaired by BMT, serial renal biopsies were carried out using B/WF1 mice before and after BMT. Donor-derived B cells and macrophages with normal functions developed two weeks (wks) after BMT. At this stage, the macrophages did not show immune complex (IC) clearance activity. 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 showed marked phagocytic activity; macrophages and mesangial cells were found to be responsible for the clearance of ICs, whereas, to our surprise, epithelial cells were found to be responsible for the repair of injured basement membranes. These findings suggest that T cells with normal functions, which have the capacity to activate macrophages, mesangial cells and epithelial cells, play a crucial role in repairing IC-mediated glomerular damage.