FUNCTIONAL TOLERANCE IN FACIAL TISSUE ALLOGRAFT TRANSPLANTS

Abstract

O133* Aims: We introduce a hemi-facial allograft transplant model to investigate the rationale for development of functional tolerance across MHC barrier. Materials: Thirty composite hemiface transplantations were performed in 5 groups of 6 rats each. Lewis (RT1l) rats served as recipients in all groups. Isograft transplants were performed in Group 1. Transplants from semi-allogenic LBN(RT1l+n) (Group 2) and fully-allogenic ACI(RT1a) (Group 3) donors served as allograft rejection controls. Group 4 (LBN donors) and Group 5 (ACI donors) received CsA monotherapy of 16 mg/kg/day for 1 week, tapered to 2 mg/kg/day over 4 weeks and continued at this dose level thereafter. Signs of graft rejection were evaluated daily. Flow cytometry evaluated donor specific chimerism for MHC class I RT1n and RT1a antigens at days 21 and 63 post-transplant. Mixed lymphocyte reaction (MLR) for donor specific tolerance was tested at day 160 post-transplant. Histological grading of graft rejection was evaluated after H-E staining. Results: Isograft controls survived indefinitely. All non-treated allografts were rejected within 5 to 9 days post-transplant. 83% of face-transplant recipients from LBN donors and 67% from ACI donors did not show any signs of rejection up to 270 days and 200 days respectively. The rejection signs were reversed by CsA dose adjustments in remaining allografts. Donor specific chimerism at day 63 in LBN recipients showed 3.39% CD4/RT1n, 1.01% CD8/RT1n T-lymphocytes and 3.54% CD45RA/RT1n B-lymphocytes; and in ACI recipients 10.55% CD4/RT1a and 4.59% CD8/RT1a T-lymphocytes. MLR assay at day 160 post-transplant revealed suppressed responses against LBN donor antigens in Group 4, but moderate reactivity to the ACI donor antigens in Group 5. Grade II rejection pattern was established in skin biopsies of rejecting LBN and ACI recipients at days 140 and 180 post-transplant. Conclusion: Functional tolerance was induced in hemifacial allograft transplants across MHC barrier under CsA monotherapy protocol. This was associated with the presence of donor specific chimerism in T- and B-cell subpopulations.