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


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Abstract

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 vivoCD8-mediated clearance of alloprimed B cells was also FasL- and perforin-dependent.In vitrodata 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.

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