Alloprimed CD8 + T Cells Regulate Alloantibody and Eliminate Alloprimed B Cells Through Perforin‐ and FasL‐Dependent Mechanisms

While it is well known that CD4 + T cells and B cells collaborate for antibody production, our group previously reported that CD8 + T cells down‐regulate alloantibody responses following transplantation. However, the exact mechanism involved in CD8 + T cell–mediated down‐regulation of alloantibody remains unclear. We also reported that alloantibody production is enhanced when either perforin or FasL is deficient in transplant recipients. Here, we report that CD8 + T cell–deficient transplant recipient mice (high alloantibody producers) exhibit an increased number of primed B cells compared to WT transplant recipients. Furthermore, CD8 + T cells require FasL, perforin and allospecificity to down‐regulate posttransplant alloantibody production. In vivo CD8‐mediated clearance of alloprimed B cells was also FasL‐ and perforin‐dependent. In vitro data demonstrated that recipient CD8 + T cells directly induce apoptosis of alloprimed IgG1 + B cells in co‐culture in an allospecific and MHC class I‐dependent fashion. Altogether these data are consistent with the interpretation that CD8 + T cells down‐regulate posttransplant alloantibody production by FasL‐ and perforin‐dependent direct elimination of alloprimed IgG1 + B cells.