Beneficial effects of bone marrow transplantation on the serological manifestations and kidney pathology of experimental systemic lupus erythematosus.
We have recently shown, using allogeneic bone marrow transplantation (BMT), that susceptibility of mice to the induction of experimental systemic lupus erythematosus (SLE) is determined by bone marrow (BM)-derived cells. In the present study we investigated the ability of BMT to cure mice already afflicted with this disease. We found that transplantation of SLE-diseased mice, with T-cell-depleted BM cells either from an SLE-resistant or from an SLE-susceptible donor, caused a significant reduction in the levels of anti-16/6 Id, 16/6 Id+, anti-ssDNA, and anti-dsDNA autoantibodies, compared to untreated SLE-afflicted mice. Interestingly, the reduction caused by the BMT of SLE-susceptible donor cells in the levels of the two former antibodies was significantly milder than the reduction caused by BMT of SLE-resistant cells. In contrast, the reduction in the levels of anti-ssDNA and anti-dsDNA antibodies, following BMT of cells from SLE-susceptible donors, did not differ from that caused by transplantation of BM cells from SLE-resistant donors. Following the transplantation of SLE-resistant but not of SLE-susceptible BM cells, a significant reduction was observed in the frequency of mice suffering from SLE-related immune complex deposits in their kidneys. If performed at advanced stages of the disease, transplantation of SLE-resistant BM cells into experimental SLE-diseased mice still led to a reduction in the levels of SLE-related autoantibodies, although to a lesser extent, but failed in improving kidney pathology. In conclusion, our data demonstrate that bone marrow transplantation has a beneficial effect on mice afflicted with experimental SLE.
Levite
M
M
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Zinger
H
H
Zisman
E
E
Reisner
Y
Y
Mozes
E
E
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D016026:Bone Marrow Transplantation / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011863:Radioimmunoassay; D014916:Whole-Body Irradiation
D000936:Antigen-Antibody Complex; D001323:Autoantibodies