Alloantigen-specific immunoregulatory function of anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways / 中国免疫学杂志

ABSTRACT

Objective:To investigate alloantigen-specific immunoregulatory function and phenotype of anergic cells induced by combined anti-CD154 and anti-CD80 monocolonal antibody(mAb) blocking.Methods:Anergic cells were generated in vitro by the addition of anti-CD154 and anti-CD80 mAbs to primary MLR (mixed lymphocyte reaction) consisting of BALB/C as responder and C3H as stimulator. Anergic or control cells were added to a newly formed MLR of naive BALB/C spleenocytes against the original (C3H) stimulator spleenocytes in assessing the regulatory capacity of anergic cells .Antigen specificity of the regulatory phenomenon was examined in MLR performed with third-party stimulator spleenocytes(C57BL/6J). To test the reversal condition of anergic cells,irradiated C3H spleenocytes,or recombinant mouse interleukin-2 (rmIL-2),or both C3H spleenocytes and rmIL-2 were added to the anergic cells. Anergic cells were phenotypically analyzed by double labeling procedure. Results:Anergic cells strongly suppressed the proliferation of naive BALB/C spleenocytes against the original (C3H) stimulator spleenocytes in a dose-dependent manner,but they failed to suppress the proliferation of naive BALB/C spleenocytes against the third-party stimulator spleenocytes(C57BL/6J).The anergic state was reversed by both original(C3H)stimulator and the addition of exogenous IL-2. There was an increased number of CD25 +CD4 +T cells observed in anergic cells,whereas there was no difference of CD45RB low CD4 + and CD28-CD8 +T cells between anergic and control cells.Conclusion:Anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways possess the alloantigen-specific immunoregulatory function and suppress the lymphocyte proliferation via infectious tolerance.