Antibody‐suppressor CXCR5+CD8+ T cellular therapy ameliorates antibody‐mediated rejection following kidney transplant in CCR5 KO mice. Issue 6 (15th February 2022)

• Record Type: Journal Article
• Authors: Zimmerer, Jason M.; Han, Jing L.; Peterson, Chelsea M.; Zeng, Qiang; Ringwald, Bryce A.; Cassol, Clarissa; Chaudhari, Sachi; Hart, Madison; Hemminger, Jessica; Satoskar, Anjali; Abdel‐Rasoul, Mahmoud; Wang, Jiao‐Jing; Warren, Robert T.; Zhang, Zheng J.; Breuer, Christopher K.; Bumgardner, Ginny L.
• Is Part Of: American journal of transplantation. Volume 22:Issue 6(2022)
• Page Start: 1550
• Page End: 1563
• Publication Date: 2022-02-15
• Subjects: alloantibody -- antibody‐mediated (ABMR) -- chemokine receptors -- chemokines -- immune regulation -- immunobiology -- kidney transplantation -- nephrology -- rejection -- science -- T cell biology -- translational research; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.16988
• Languages: English
• ISSNs: 1600-6135

Abstract

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. Abstract : 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.