[Induction of skin allograft tolerance in mice by using anti-alphabeta T cell receptor and anti-CD80 monoclonal antibodies combined with bone marrow transfusion].

OBJECTIVE

To explore the role of anti-alphabeta T cell receptor (TCR) and anti-CD80 monoclonal antibodies (mAbs) combined with donor bone marrow cells (BMCs) infusion in the induction of murine skin allografts tolerance.

METHODS

On day 0, 2 x 10(8) BMCs of BALB/c mice were injected into recipient C57BL/6 mice via the tail vein, meanwhile, an intraperitoneal injection of TCRalphabeta mAb (500 microg) was given. On day 2, CD80 mAb was administered intraperitoneally. Skin grafting was performed on day 6. Delayed type hypersensitivity (DTH), mixed lymphocyte reaction (MLR), IL-2 reverse assay of MLR, adoptive transfer assay and chimerism detection were performed at different time points and tolerance mechanisms were investigated.

RESULTS

The mean survival time (MST) of BALB/c skin allografts in C57BL/6 recipients that were treated by anti-TCRalphabeta and anti-CD80 mAbs combined with donor BMCs infusion was 70 days. DTH and MLR assay indicated that the tolerant mice displayed significant hyporesponsiveness. The result of IL-2 reverse test showed that clone anergy was probably involved in the formation of tolerance in the tolerant C57BL/6 mice. In vivo and in vitro adoptive transfer assay, suppressive activity in the spleens of tolerant C57BL/6 mice was observed. Chimerism existed in both the thymus and spleen of the tolerant C57BL/6 mice. The chimerism level gradually declined with time.

CONCLUSION

Treatment of anti-TCRalphabeta and anti-CD80 mAbs combined with donor BMCs infusion can successfully induce a long-term tolerance in BALB/c mice to C57BL/6 skin graft. Multiple mechanisms, including clone anergy, suppressor cells and chimerism are involved in the tolerance.