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Allogenic Mixed Chimerism Induced by Nonlymphoablative Regimen Including Donor BMT with Low‐Dose TBI and Anti‐CD40L Cured Proliferative Glomerulonephritis in Lupus Mice
Author(s) -
TAKEUCHI EMIKO,
TAKEUCHI YASUO
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1423.038
Subject(s) - medicine , immunology , glomerulonephritis , regimen , systemic lupus erythematosus , cyclophosphamide , kidney , chemotherapy , disease
: 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 × 10 6 BALB/c (H‐2 d ) 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.