Induction of skin allograft tolerance in mice by using anti-?? T cell receptor and anti-CD80 monoclonal antibodies combined with bone marrow transfusion
- VernacularTitle:抗T细胞受体??单抗和抗CD80单抗联合供体骨髓移植诱导小鼠皮肤移植耐受
- Author:
Jie HAO
;
Jiawang LIU
;
Xiang GAO
;
Guohong YUAN
;
Shusheng XIE
- Publication Type:Journal Article
- Keywords:
Antibodies,monoclonal;
Chimera;
Bone marrow cells;
Skin transplantation;
Transplantation tolerance
- From:
Journal of Peking University(Health Sciences)
2003;0(04):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the role of anti-?? 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?10~8 BMCs of BALB/c mice were injected into recipient C57BL/6 mice via the tail vein,meanwhile,an intraperitoneal injection of TCR?? mAb(500 ?g) 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-TCR?? 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-TCR?? 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.