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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.

Authors: Takeuchi, E  Takeuchi, Y 
Citation: Takeuchi E and Takeuchi Y, Ann N Y Acad Sci. 2007 Sep;1110:362-7.
Pubmed: (View Article at PubMed) PMID:17911451
DOI: Full-text: DOI:10.1196/annals.1423.038

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.

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RGD ID: 7248430
Created: 2013-08-02
Species: All species
Last Modified: 2013-08-02
Status: ACTIVE



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