Blockade of CD40/CD154 and B7/CD28 costimulatory pathways induces alloantigen-specific anergic state / 中华器官移植杂志

ABSTRACT

Objective To investigate the possibility of inducing anergy by blocking the CD40/CD154 and B7/CD28 costimulatory pathways and the reversal condition of anergic cells. Methods Splenocyte proliferation in primary mixed lymphocyte reaction (MLR) consisting of BALB/c as responder and C3H as stimulator was measured by the addition of different levels of anti-CD154 and anti-CD80 monocolonal antibody (mAb). To test the reversal condition of anergic cells induced by combined anti-CD154 and anti-CD80 mAbs blocking, C3H or C57BL/6J spleenocytes were irradiated, or different concentrations of recombinant mouse interleukin-2 (rmIL-2), or both C3H splenocytes and rmIL-2 were added to the anergic cells. Results The proliferation of anergic cells treated with both mAbs in the primary MLR was strongly inhibited in a dose-dependent manner. The cells proliferated in response to third party (C57BL/6J) stimulator. The cells did not respond to original (C3H) stimulator, and they also failed to proliferated in response to the addition of exogenous IL-2. Furthermore, the anergic state was reversed by both original (C3H) stimulator and the addition of exogenous rmIL-2. Conclusion The blockade of CD40/CD154 and B7/CD28 costimulatory pathways induces alloantigen-specific anergy, and the anergic state can be reversed by both antigen restimulation and the addition of exogenous IL-2.