Study on the induction of skin transplantation tolerance in mice by anti-TCRαβ monoclonal antibody combined with high dose of donor bone marrow cells infusion

Objective 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. Methods On day 0, 2×10 8 bone marrow cells (BMC) of BALB/c mouse (H-2 d) were injected into recipient C57BL/6 (H-2 b, B6) mice via the tail vein, meanwhile, an intraperitoneal injection of anti-TCRαβ monoclonal antibody (500μg) was given. Skin grafting was performed on day 6. DTH, MLR, IL-2 reverse assay of MLR and adoptive transfer assay were performed at different time points and tolerance mechanisms were investigated. Results The mean survival time (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 in other groups ( P 0.001). DTH and MLR assay indicated that the tolerant mice displayed significant hyporesponsivness against donor antigen ( P 0.001). 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. Conclusion Treatment of anti-TCRαβ monoclonal antibody combined with high dose of donor bone marrow cells infusion can successfully induce a long-term tolerance in BALB/c mice to B6 skin graft. Multiple mechanisms, including clone anergy and suppressor cells were involved in the tolerence.