Antibody‐suppressor CXCR5+CD8+ T cellular therapy ameliorates antibody‐mediated rejection following kidney transplant in CCR5 KO mice

CCR5 KO kidney transplant (KTx) recipients are extraordinarily high alloantibody producers and develop pathology that mimics human antibody‐mediated rejection (AMR). C57BL/6 and CCR5 KO mice (H‐2b) were transplanted with A/J kidneys (H‐2a); select cohorts received adoptive cell therapy (ACT) with alloprimed CXCR5+CD8+ T cells (or control cells) on day 5 after KTx. ACT efficacy was evaluated by measuring posttransplant alloantibody, pathology, and allograft survival. Recipients were assessed for the quantity of CXCR5+CD8+ T cells and CD8‐mediated cytotoxicity to alloprimed IgG+ B cells. Alloantibody titer in CCR5 KO recipients was four‐fold higher than in C57BL/6 recipients. The proportion of alloprimed CXCR5+CD8+ T cells 7 days after KTx in peripheral blood, lymph node, and spleen was substantially lower in CCR5 KO compared to C57BL/6 recipients. In vivo cytotoxicity towards alloprimed IgG+ B cells was also reduced six‐fold in CCR5 KO recipients. ACT with alloprimed CXCR5+CD8+ T cells (but not alloprimed CXCR5−CD8+ or third‐party primed CXCR5+CD8+ T cells) substantially reduced alloantibody titer, ameliorated AMR pathology, and prolonged allograft survival. These results indicate that a deficiency in quantity and function of alloprimed CXCR5+CD8+ T cells contributes to high alloantibody and AMR in CCR5 KO recipient mice, which can be rescued with ACT. Adoptive cellular therapy of antibody‐suppressor CD8+ T cells (alloprimed CXCR5+CD8+ T cells) into high alloantibody‐producing murine kidney transplant recipients reduced alloantibody, ameliorated pathology of antibody‐mediated rejection, and prolonged allograft survival.