Purpose: Transplantation of vascularized skin allografts such as the groin flaps could have important clinical applications for wound coverage. The need for life long immunosuppression is precluding the routine use of skin allografts. In this study, we investigated the effect of the short 7 days protocols of immunosuppressive monotherapies and combined therapies on the extension of survival of vascularized skin allografts in the rat experimental model.

Methods: Thirty transplantations of vascularized skin (groin) allografts across strong MHC barrier were performed between ACI (RT1^a) donors and LEW (RT1^l) recipients in 6 groups. Isograft (n=6) and allograft rejection control (n=6) groups received no treatment. Treated groups received either rat a b TCR (n=6) or CsA (n=6) monotherapies or combination of a b TCR+CsA (n=6) for 7 days only. The survival of the flaps was evaluated by the clinical and histopathological examination. The efficacy of immunosuppressive treatment and the level of donor specific chimerism in the peripheral blood of recipients were determined by flow cytometry (FC).

Results: Indefinite flap survival was observed in isograft controls. Allograft controls were rejected between 5-7 days posttransplant. The monotherapy of a b TCR and CsA extended survival up to 11.6±3.0, and 15.8±2.3 days respectively. The combined a b TCR+CsA therapy prolonged the vascularized skin allografts survival up to 58.5±28.1 (p<0.05) days after transplantation. FC analysis revealed high efficacy of the immunosuppressive treatment and development of donor specific chimerism in the peripheral blood of long-term VSA survivors, which ranged between 3.2-4.6% for CD4+/RT1^a+ double positive T cells, 1.5-2.3% for CD8+/RT1^a+ cells and 0.9-1.4% for CD45RA+/RT1^a+ B cell subpopulation.

Conclusions: In this study, significant extension of vascularized skin allografts survival across strong MHC barrier was achieved under combined a b -TCR+CsA protocol without preconditioning of the recipient. The augmentation of survival was directly associated with the presence of lymphoid chimerism in the peripheral blood of vascularized skin allograft recipients. The mechanisms responsible for hyporesponsiveness of alloreactive cells in this model need to be elucidated.