Induction of tolerance in fully MHC disparate composite tissue allografts

Abstract

Induction of donor-specific tolerance in composite tissue allografts (CTA) continues to be one of the most challenging goals. In our previous study, using combined TCR mAb + CsA treatment we induced tolerance between LBN donors (RTln/l; FI) and Lewis recipients (LEW; RTII) in CTAs model. The primary aim of this study is to induce tolerance in the fully MHC mismatched allograft recipients under combined alpha-betaTCR+CSA protocol. Thirty transplantations across strong MHC barrier between BrownNorway donors (RTln) and LEW recipients were performed. The animals from experimental groups received for 7 days either rat TCR and CsA or a combination of alpha-betaTCR+CsA, The immunosuppressive treatment efficacy and chimerism was monitored by flow cytometry. The survival > lOOdays was noted in allograft recipients treated with combination of TCXUCsA. Flow cytometry analysis demonstrated mixed chime&m in the periphery of tolerated recipients. Donor specific tolerance was confirmed by rejection of the third-party skin graft and by MLR. Tolerance can be induced in the short term using a TCRKsA protocol in the fully mismatched CTAs. Stable mixed chimerism can be achieved without myeloahlative bone marrow modifications of the recipients.