Development of donor-specific chimerism and tolerance in composite tissue allografts under αβ-T-cell receptor monoclonal antibody and cyclosporine a treatment protocols
✍ Scribed by Kagan Ozer; Dariusz Izycki; Maciej Zielinski; Maria Siemionow
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 337 KB
- Volume
- 24
- Category
- Article
- ISSN
- 0738-1085
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✦ Synopsis
Abstract
Recently, we induced donor‐specific tolerance to rat hindlimb allografts under a 35‐day course of αβ‐T‐cell receptor monoclonal antibody (αβ‐TCR mAb) and cyclosporine A (CsA). In this report, we investigated the role of shorter αβ‐TCR/CsA protocols on tolerance induction. We performed 52 hindlimb transplantations, between Lewis‐Brown‐Norway (LBN, F1) donors and Lewis recipients to test the impact of 21‐, 7‐, and 5‐day protocols of combined αβ‐TCR/CsA treatment on tolerance induction. Donor‐specific tolerance and immunocompetence were tested by mixed lymphocyte reaction (MLR) in vitro and by standard skin grafting in vivo. The efficacy of immunosuppressive protocol and donor‐specific chimerism was assessed by flow cytometry. All transplants under 5, 7, and 21 days of combined αβ‐TCR/CsA therapy survived over 350 days. Clinical tolerance and immunocompetence were confirmed by skin grafting in vivo and MLR in vitro. Flow cytometry revealed a high level of donor chimerism in the peripheral blood of long‐term survivors. The extention of survival of limb allografts and allo‐unresponsiveness were directly associated with the development of stable chimerism in the tolerant recipients. © 2004 Wiley‐Liss, Inc.