IMR Press / FBL / Volume 12 / Issue 8 / DOI: 10.2741/2292

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Small bowel transplantation tolerance achieved by costimulatory blockade leading to mixed chimerism
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1 Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, 755-8505, Japan
Front. Biosci. (Landmark Ed) 2007, 12(8), 3017–3023;
Published: 1 May 2007

We evaluated mixed chimerism with costimulatory blockade for the achievement murine allogeneic small bowel transplantation (SBTx) tolerance. B6 mice received various combinations of anti-CD8 (day -2) and anti-CD154 mAbs with or without 3Gy total body irradiation (TBI) (day -1), and 20 x 106 fully MHC-mismatched B10.A bone marrow cells (BMC, day -1). Heterotopic SBTx was performed on day 0. Chimerism in peripheral blood was followed by flow cytometric (FCM) analysis and the frequency of TCR Vβ usage was determined by FCM to assess deletion of donor-reactive T cells. All animals without any treatment (n=6) showed acute rejection within 18 days after transplantation. Mice treated with anti-CD8 and anti-CD154 mAbs alone rejected their grafts within 100 days after transplantation (n=10). Mice treated with anti-CD8 and anti-CD154 mAbs, TBI, and BMT achieved long-term multilineage mixed chimerism and accepted small bowel allografts permanently (>350 days) without any evidence of graft-versus-host disease(n=11). There was specific deletion of donor-reactive cells and skin was accepted as allografts from B10.A donors, but 3rd party B10.BR skin was rejected. Donor-specific tolerance was achieved by inducing mixed chimerism with costimulatory blockade in murine SBTx recipients. This approach which provides a reliable method to induce SBTx tolerance, has potential clinical applications.

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