Study on the Induction of Skin Transplantation Tolerancein Mice by Anti-TCRαβ mAb Combined with Donor Bone Marrow Cells Infusion

To explore the role of anti-TCRαβ monoclonal antibody combined with high dose of donor bone marrow cells infusion in the induction of murine skin allografts tolerance. 2×10 8 bone marrow cells(BMC) Of BALB/c mice (H-2 d) were injected into recipient C57BL/6( H-2 b,B6) mice via the tail vein on day 0,meanwhile,an intraperitoneal injection of anti-TCRαβ monoclonal antibody(500 μg)was given.Skin grafting was performed on day 6 and DTH, MLR,IL-2 reverse assay of MLR, adoptive transfer assay and chimerism were performed at different time points to investigate the mechanism of tolerance. It was found that the mean survivaltime (MST) of BALB/c skin allografts in B6 recipients that were treated by anti-TCRαβ monoclonal antibody combined with high dose of donor bone marrow cells infusion was 50.4 days,which was significantly longer than that of other groups.DTH and MLR assay indicated that the tolerant mice displayed significant hyporesponsivness against donor antigen(P0.001).The result of IL-2 reverse test showed that clone anergy was probably involved in the' formation of tolerance in the tolerant B6 mice.In vivo and in vitro adoptive transfer assay,suppressive activity in the spleens of tolerant B6 mice was observed.Chimerism exists in both the thymus and spleen of the tolerant B6 mice.The percentage of cells of BALB/c origin in the spleen of B6 mice in the tolerant mice was 15.86%,10.57%and 1.77% on day 15,30 and 70 after skin grafting,and in the thymus was 8.19%,5.72% and 1.87%,respectively.The chimerism level gradually declined with time.It concludes that treatment of anti-TCRαβ monoclonal antibody combined with high dose of donor bone marrow cells infusion can successfully induce a long-term tolerancein BALB/c mice to B6 skin graft and multiple mechanisms,including clone anergy,suppressor cells and chimerism were involved in the tolerance induction.