Anti-rejection effects of CTLA-4 Ig fusion protein on cardiac allografts in mice and its mechanism in vivo / 第二军医大学学报

ABSTRACT

Objective: To determine the anti rejection effects of CTLA 4 Ig fusion protein on cardiac allografts in mice and to discuss its mechanism in vivo . Methods: BALB/c recipients were performed cervical heterotopic heart transplantation to receive C57BL/6 donor hearts with a cuff technique. BALB/c recipients were intraperitoneally injected with CTLA 4 Ig [100 ?g/d?15 times], control immunoglobins and PBS to observe the survival time of allografts with ECG. The hyporesponsiveness of splenic T cell, the polarization of the T subsets were analyzed after the recipients treated with CTLA 4 Ig. Results: After treated with CTLA 4 Ig, the survival of cardiac grafts was significantly prolonged compared with the control groups, and more than 40% cardiac grafts survived over 2 months. The splenic T cells isolated from recipients did not respond to restimulation of donor splenocytes in MLR, but did exhibit the capacity to proliferate in response to C3H splenocytes(third party).The levels of IL 2 and IFN ? decreased and the level of IL 10 increased in CTLA 4 Ig treated mice. Conclusion: Administration of CTLA 4 Ig can induce donor specific tolerance, which induce T subsets to polarize toward Th2 subset and hyporesponsiveness to alloantigen, and prolong the survival time of the cardiac grafts effectively. [