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Autoreactive T cell profiles are altered following allogeneic islet transplantation with alemtuzumab induction and re‐emerging phenotype is associated with graft function

Sabbah, S; Liew, A; Brooks, AM; Kundu, R; Reading, JL; Flatt, A; Counter, C; ... Tree, TIM; + view all (2020) Autoreactive T cell profiles are altered following allogeneic islet transplantation with alemtuzumab induction and re‐emerging phenotype is associated with graft function. American Journal of Transplantation 10.1111/ajt.16285. (In press). Green open access

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Abstract

Islet transplantation is an effective therapy for life‐threatening hypoglycemia, but graft function gradually declines over time in many recipients. We characterized islet‐specific T cells in recipients within an islet transplant program favoring alemtuzumab (ATZ) lymphodepleting induction and examined associations with graft function. Fifty‐eight recipients were studied: 23 pretransplant and 40 posttransplant (including 5 with pretransplant phenotyping). The proportion with islet‐specific T cell responses was not significantly different over time (pre‐Tx: 59%; 1–6 m posttransplant: 38%; 7–12 m: 44%; 13–24 m: 47%; and >24 m: 45%). However, phenotype shifted significantly, with IFN‐γ–dominated response in the pretransplant group replaced by IL‐10–dominated response in the 1–6 m posttransplant group, reverting to predominantly IFN‐γ–oriented response in the >24 m group. Clustering analysis of posttransplant responses revealed two main agglomerations, characterized by IFN‐γ and IL‐10 phenotypes, respectively. IL‐10–oriented posttransplant response was associated with relatively low graft function. Recipients within the IL‐10+ cluster had a significant decline in C‐peptide levels in the period preceding the IL‐10 response, but stable graft function following the response. In contrast, an IFN‐γ response was associated with subsequently decreased C‐peptide. Islet transplantation favoring ATZ induction is associated with an initial altered islet‐specific T cell phenotype but reversion toward pretransplant profiles over time. Posttransplant autoreactive T cell phenotype may be a predictor of subsequent graft function.

Type: Article
Title: Autoreactive T cell profiles are altered following allogeneic islet transplantation with alemtuzumab induction and re‐emerging phenotype is associated with graft function
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/ajt.16285
Publisher version: https://doi.org/10.1111/ajt.16285
Language: English
Additional information: Copyright © 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC 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‐NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Keywords: autoantibody, basic (laboratory) research/science, clinical research/practice, immunobiology, islet transplantation, islets of Langerhans, monitoring: immune, T cell biology
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 > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10112956
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