216. Development of donor specific chimerism and tolerance in composite tissue allografts under ab-t cell receptor monoclonal antibody and cyclosporine a treatment protocols

Abstract

Purpose Recently, we induced donor specific tolerance to rat hind-limb allografts under 35 days course of ab TCR mAb and Cyclosporine A. In this report, we investigated the role of shorter ab-TCR/CsA protocols on the tolerance induction. Materials and Methods We performed fifty-two hind-limb transplantations, between Lewis-Brown-Norway (LBN, F1) donors and Lewis recipients to test the impact of 21, 7 and 5 day protocols of combined ab-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. Results All transplants under 5,7, and 21 days of combined ab-TCR/CsA therapy survived over 350 days. Clinical tolerance and immunocompetence were confirmed by skin grafting in vivo and MLR in vitro. Flow cytornetry revealed high level of donor chimerism in the peripheral blood of the long term survivors. Conclusion The extention of survival of limb allografts and allounresponsiveness were directly associated with the development of stable chimerism in the tolerated recipients.