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

Autor: Zimmerer JM; Department of Surgery, Comprehensive Transplant Center, The Ohio State University, Columbus, Ohio, USA., Han JL; Department of Surgery, Comprehensive Transplant Center, The Ohio State University, Columbus, Ohio, USA.; Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, Ohio, USA., Peterson CM; Department of Surgery, Comprehensive Transplant Center, The Ohio State University, Columbus, Ohio, USA., Zeng Q; Center for Regenerative Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA., Ringwald BA; Medical Student Research Program, The Ohio State University College of Medicine, Columbus, Ohio, USA., Cassol C; Department of Pathology, The Ohio State University, Columbus, Ohio, USA., Chaudhari S; Department of Surgery, Comprehensive Transplant Center, The Ohio State University, Columbus, Ohio, USA., Hart M; Department of Surgery, Comprehensive Transplant Center, The Ohio State University, Columbus, Ohio, USA., Hemminger J; Department of Pathology, The Ohio State University, Columbus, Ohio, USA., Satoskar A; Department of Pathology, The Ohio State University, Columbus, Ohio, USA., Abdel-Rasoul M; Center for Biostatistics, The Ohio State University, Columbus, Ohio, USA., Wang JJ; Department of Surgery, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Warren RT; Department of Surgery, Comprehensive Transplant Center, The Ohio State University, Columbus, Ohio, USA., Zhang ZJ; Department of Surgery, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Breuer CK; Center for Regenerative Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA., Bumgardner GL; Department of Surgery, Comprehensive Transplant Center, The Ohio State University, Columbus, Ohio, USA.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2022 Jun; Vol. 22 (6), pp. 1550-1563. Date of Electronic Publication: 2022 Feb 15.
DOI: 10.1111/ajt.16988
Abstrakt: 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.
(© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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