Histoincompatibility-associated differences in the phenotypes of murine cardiac allograft infiltrating T cells

Mechanisms of graft rejection may be governed in part by the kind and degree of histocompatibility differences between donor and recipient. Cardiac allograft rejection was studied in three murine models selected to provide disparity at different major histocompatibility complex (MHC), minor lymphocyte stimulating (Mls) and other minor histocompatibility loci. Graft survival for the A.TL to A.TH combination (M3) was significantly longer (median day of rejection 15.0 days) than both the B10.A to AKR (M2) or the C57BL/6 to C3H/HeN (M1) donor-recipient combinations (median days of rejection: 9.0 days and 9.0 days respectively; P < 0.001). The infiltration of grafts by T cells was examined by removal of grafts serially post-transplantation and culturing mechanically disrupted graft tissue with interleukin-2 (IL-2). Recovery of T cells by this method revealed highly reproducible characteristics (kinetic and phenotypic), unique to each donor-recipient combination. Cultures from M1 and M2 grafts had differing CD4/CD8 T-cell ratios at days 2 (1.8 versus 0.7, respectively) and 4 (1.6 versus 0.1, respectively) post-transplantation. The M3 model differed from M2 (at days 4, 8 and 10) and from M1 (at days 8 and 10). At these times, cultures of M3 grafts contained a significantly increased percentage of CD4 cells and significantly decreased percentage of CD8 cells (CD4/CD8 ratios 0.9-1.3) by comparison with M1 (CD4/CD8 ratios 0.02-0.04) and M2 (CD4/CD8 ratios 0.1-0.02). Long-surviving M3 grafts (greater than 30 days post-transplantation) were compared with grafts removed immediately upon cessation of graft function (days 14, 15 and 18 post-transplantation). There was a significant difference between these groups in the ratios of CD4/CD8 T-cell ratios (1.1 versus 0.4, respectively). This study suggests that the cellular rejection mechanism of a graft is a variable process driven by the individual histocompatibility antigen disparity between donor and recipient. These findings may have diagnostic and therapeutic applications in organ transplantation.