Prolongation of allograft survival by passenger donor regulatory T cells.

Autor: Harper IG; Department of Surgery, School of Clinical Medicine, University of Cambridge, Cambridge, UK., Gjorgjimajkoska O; Department of Surgery, School of Clinical Medicine, University of Cambridge, Cambridge, UK., Siu JHY; Department of Surgery, School of Clinical Medicine, University of Cambridge, Cambridge, UK., Parmar J; Department of Cardiothoracic Transplantation, Papworth Hospital, Cambridge, UK., Mulder A; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands., Claas FHJ; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands., Hosgood SA; Department of Surgery, School of Clinical Medicine, University of Cambridge, Cambridge, UK., Nicholson ML; Department of Surgery, School of Clinical Medicine, University of Cambridge, Cambridge, UK., Motallebzadeh R; Centre for Surgical Innovation, Organ Repair & Transplantation, University College London, London, UK.; Centre for Transplantation, Department of Renal Medicine, University College London, London, UK.; Institute of Immunity and Transplantation, University College London, London, UK., Pettigrew GJ; Department of Surgery, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
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] 2019 May; Vol. 19 (5), pp. 1371-1379. Date of Electronic Publication: 2019 Feb 05.
DOI: 10.1111/ajt.15212
Abstrakt: Tissue resident lymphocytes are present within many organs, and are presumably transferred at transplantation, but their impact on host immunity is unclear. Here, we examine whether transferred donor natural regulatory CD4 T cells (nT-regs) inhibit host alloimmunity and prolong allograft survival. Transfer of donor-strain lymphocytes was first assessed by identifying circulating donor-derived CD4 T cells in 21 consecutive human lung transplant recipients, with 3 patterns of chimerism apparent: transient, intermediate, and persistent (detectable for up to 6 weeks, 6 months, and beyond 1 year, respectively). The potential for transfer of donor nT-regs was then confirmed by analysis of leukocyte filters recovered from ex vivo normothermic perfusion circuits of human kidneys retrieved for transplantation. Finally, in a murine model of cardiac allograft vasculopathy, depletion of donor CD4 nT-regs before organ recovery resulted in markedly accelerated heart allograft rejection and augmented host effector antibody responses. Conversely, adoptive transfer or purified donor-strain nT-regs inhibited host humoral immunity and prolonged allograft survival, and more effectively so than following administration of recipient nT-regs. In summary, following transplantation, passenger donor-strain nT-regs can inhibit host adaptive immune responses and prolong allograft survival. Isolated donor-derived nT-regs may hold potential as a cellular therapy to improve transplant outcomes.
(© 2018 The Authors American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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