Treatment of autoimmune diseases in MRL/lpr mice by allogenic bone marrow transplantation plus adult thymus transplantation.

MRL/lpr mice (H-2(k)) with Fas gene mutation develop severe autoimmune diseases, and their haematolymphoid cells such as bone marrow and spleen cells showed a low apoptotic activity by irradiation. Therefore, conventional bone marrow transplantation (BMT) cannot be used to treat autoimmune diseases in these mice (chimeric resistance). In the present study, we examine the effects of additional adult thymus transplantation (TT) from the same donor on successful BMT. When the MRL/lpr mice were lethally irradiated (9 x 5Gy) and reconstituted with 3 x 10(7) of C57BL/6 mouse (H-2b) bone marrow cells (BMCs) in conjunction with TT, the mice significantly survived long term and showed a high donor-derived chimerism in comparison with those treated with BMT alone. Interestingly, the numbers of not only donor-derived T cells but also B cells increased significantly in the mice treated with BMT plus TT, even at the early phase of BMT. The number of aberrant CD3+B220+ cells decreased significantly, and the numbers of lymphocyte subsets were also normalized 4 weeks after the treatment. Finally, the autoimmune diseases in MRL/lpr mice could be cured by BMT with TT. These results indicate that the combination of BMT plus TT can overcome the chimeric resistance and treat the autoimmune diseases in MRL/lpr mice.