Allogenic mixed chimerism prevented autoimmune thrombocytopenia in BXSB lupus mice receiving donor BMT with nonlymphoablative conditioning of low-dose TBI and anti-CD40L mAb

Objectives: We have demonstrated that allogeneic bone marrow transplant (BMT) with low-dose total body irradiation (TBI) and anti-CD40L mAb without lymphoablative treatment achieved durable mixed chimerism and permanent donor-specific tolerance. Also, allogeneic mixed chimerism induced by anti-CD40L-containing regimen overcomes both alloand autoimmunity in NOD mice. BXSB mice with a lymphoproliferative disorder, splenomegaly, glomurulonephritis, and thrombocytopenia are adequate models of human systemic lupus erythematosus (SLE). Prolonged immunosuppressive therapy is required for treatment of autoimmune thrombocytopenia in human disease. We investigated whether or not allogenic mixed chimerism induced by nonlymphoablative regimen cured autoimmune thrombocytopenia in BXSB lupus mice. Materials and Methods: Age-matched male BXSB (H-2) mice were received 20 × 10 BALB/c (H2) BM cells. 4 Gy TBI on day -1 and anti-CD40L mAb (2 mg) on day 0 to BMT was given. Skin grafting (donor BALB/c and third party C3H/He) was performed one day after BMT to assess tolerance. Chimerism in peripheral blood was followed by flow cytometric analysis. Peripheral blood counting was performed by autoanalyzer. Antiplatelet antibody was detected by flow cytometric analysis. Results: 4 Gy TBI on day -1 with anti-CD40L mAb and BMT on day 0 allowed induction of high levels of multilineage mixed chimerism. No clinical signs of graft versus host disease (GVHD) were observed. There was significant difference in number of platelets between chimeric BXSB mice and untreated BXSB mice. The antiplatelet antibodies could be detected in BXSB mice, but only scarcely detected in mixed chimeric BXSB mice. Conclusions: Allogenic mixed chimerism achieved by BMT with less toxic, nonlymphoablative conditioning regimen, which induces donor specific tolerance without GVHD, improved the lymphoproliferative disorder and prevented thrombocytopenia in BXSB lupus mice without immunosuppressive therapy.