Long-Term Survival of Composite Hemiface/Mandible/Tongue Allografts Correlates With Multilineage Chimerism Development in the Lymphoid and Myeloid Compartments of Recipients

Background. To maximize aesthetic and functional outcomes for complex craniofacial defects, application of composite tissue allografts opens unique one-stage reconstructive option. We have assessed role of different components of the hemiface/mandible/tongue allograft on induction and maintenance of donor-specific chimerism, in correlation with allograft survival. Methods. Twenty-two composite hemiface/mandible/tongue transplantations were performed in three groups: group 1 (n=8)-isotransplantations between Lewis (LEW) rats (RT1(1))-served as controls. Group 2 (n=8)-allograft rejection controls-hemiface/mandible/tongue transplants performed across major histocompatibility complex (MHC) barrier between semiallogeneic LEW-Brown-Norway (RT1(1+n)) donors and LEW (RT1(1)) recipients without immunosuppression. Allografts in group 3 (n=6) received tapered cyclosporine A monotherapy. Assessments included monitoring of rejection, flow cytometry for donor-specific chimerism of major histocompatibility complex class I (RT1(n)) antigen, immunohistochemistry for engraftment of donor-origin cells into lymphoid organs and bone marrow (BM) compartment, and histology for hemiface/mandible/tongue architecture. Results. Isograft controls survived indefinitely; in allografts without treatment, rejection started within 5 to 7 days. Treated hemiface/mandible/tongue allotransplants survived up to 385 days, without signs of rejection or graft loss. Flap angiography confirmed intact vascularity, and computer tomography scan and histology confirmed bone viability. Donor-specific chimerism at day 125 was present for T cells (3.3% CD4/RT1(n), 1.1% CD8/RT1(n)) and B cells (6.7% CD45RA/RT1(n)). Engraftment of donor-origin cells was confirmed into BM compartment and lymphoid organs of recipients. Conclusions. We introduced a new multitissue model of composite hemiface/mandible/tongue allograft containing lymphoid and vascularized BM components. Long-term allograft survival correlated with development and maintenance of donor-specific chimerism in lymphoid organs and BM compartment.