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Prolongation of allograft survival by passenger donor regulatory T cells

Harper, I; Gjorgjimajkoska, O; Siu, JHY; Parmar, J; Mulder, A; Class, F; Hosgood, S; ... Pettigrew, G; + view all (2019) Prolongation of allograft survival by passenger donor regulatory T cells. American Journal of Transplantation 10.1111/ajt.15212. (In press). Green open access

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Abstract

Tissue resident lymphocytes are present within many organs, and are presumably transferred at transplantation, but their impact upon 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 three patterns of chimerism apparent: transient; intermediate; and persistent (detectable for up to 6 weeks, 6 months, and beyond one year, respectively). The potential for transfer of donor nT-regs was then confirmed by analysis of leucocyte 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 prior to organ retrieval 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.

Type: Article
Title: Prolongation of allograft survival by passenger donor regulatory T cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/ajt.15212
Publisher version: https://doi.org/10.1111/ajt.15212
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: © 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 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10061708
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