Trafficking of Donor-Derived Bone Marrow Correlates With Chimerism and Extension of Composite Allograft Survival Across MHC Barrier

Abstract

We proposed to evaluate differences between recipient’s immune response to vascularized skin and combined vascularized skin/bone allografts, under a 7-day αβ-TCR plus cyclosporine (CsA) treatment protocol. Thirty-six transplantations were performed in six groups: group I (isograft control-vascularized skin graft; n = 6); group II (isograft control-combined vascularized skin/bone graft; n = 6); group III (allograft rejection control group-vascularized skin graft; n = 6); group IV (allograft rejection control-combined vascularized skin/bone graft; n = 6); group V (allograft treatment-vascularized skin graft; n = 6); and group VI (allograft treatment-combined vascularized skin/bone graft; n = 6). Isograft transplantations were performed between Lewis rats and allografts were transplanted across the MHC barrier from Brown Norway to Lewis rats. In the allograft treatment group, a combined αβ-TCR+CsA protocol was applied for 7 days. All groups were compared clinically, immunologically and histologically. Statistical significance was determined with two-tailed Student’s t test. Indefinite graft survival was achieved in the isograft control group (>300 days). Allograft rejection controls rejected within 5 to 9 days posttransplant; chimerism levels were undetectable (<.5%). Allografts under the αβ-TCR+CsA protocol had significantly extended survival when skin was combined with bone (61–125 days) compared to vascularized skin allografts (43–61 days). Lymphoid macrochimerism was significantly higher in group VI than group V. Histology confirmed skin and bone viability. Combined vascularized skin/bone allografts had higher and sustained levels of donor-specific chimerism and extended allograft survival.