Allogenic mixed chimerism induced by nonlymphoablative regimen including donor BMT with low-dose TBI and anti-CD40L cured proliferative glomerulonephritis in lupus mice.
Allogeneic mixed chimerism achieved by low-dose total body irradiation (TBI) and anti-CD40L monoclonal antibody (mAb) with donor bone marrow transplantation (BMT) and host T cell depletion overcomes both allo- and autoimmunity. We investigated whether a similar regimen without T cell depletion cured diffuse proliferative glomerulonephritis. Male BXSB mice (H-2b) were injected with 20 x 10(6) BALB/c (H-2d) BM cells. When indicated, 3 Gy TBI on day -1 and anti-CD40LmAb (2 mg) on day 0 of BMT was given. Skin grafting was performed 1 day after BMT. BXSB mice were divided into four groups--I: BMT with TBI and anti-CD40LmAb; II: TBI; III: TBI and anti-CD40LmAb; and IV: no treatment. Chimerism in peripheral blood was analyzed. The kidney was examined histologically. TBI with anti-CD40LmAb and BMT allowed induction of multilineage mixed chimerism and donor-specific tolerance to skin grafts without graft-versus-host disease (GVHD). There was significant decrease in glomerular PAS-positive material deposition score, glomerular cell numbers, IgG, and C3 deposition in chimeric mice. All chimeric mice survived. Allogeneic mixed chimerism induced by a less toxic, nonlymphoablative regimen achieved allograft tolerance and cured glomerulonephritis in BXSB lupus mice.
Takeuchi
Emiko
E
Department of Clinical Investigation, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara City, Kanagawa 228-8555, Japan. emichike@med.kitasato-u.ac.jp
Takeuchi
Yasuo
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D016026:Bone Marrow Transplantation; D023201:CD40 Ligand / Q000276:immunology* / Q000627:therapeutic use*; D046528:Chimerism; D005921:Glomerulonephritis / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D007167:Immunotherapy; D008136:Longevity; D008178:Lupus Erythematosus, Cutaneous / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D014184:Transplantation, Homologous / Q000276:immunology; D014916:Whole-Body Irradiation
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D023201:CD40 Ligand