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

ABSTRACT: 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-2^b ) were transplanted with A/J kidneys (H-2^a ); 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.

SUBMITTER: Zimmerer JM 

PROVIDER: S-EPMC9177711 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature