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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

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journal contribution
posted on 09.09.2021, 09:48 by Shereen Sabbah, Aaron Liew, Augustin M Brooks, Rhiannon Kundu, James L Reading, Anneliese Flatt, Claire Counter, Pratik Choudhary, Shareen Forbes, Miranda J Rosenthal, Martin K Rutter, Stephanie Cairns, Paul Johnson, John Casey, Mark Peakman, James A Shaw, Timothy IM Tree
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.

Funding

Diabetes UK. Grant Number: 06/0003362

NHS National Commissioning Group

Juvenile Diabetes Research Foundation. Grant Number: 17-2011-602

History

Citation

American Journal of Transplantation, Volume 21, Issue 3, March 2021, Pages 1027-1038

Author affiliation

Department of Cardiovascular Sciences, University of Leicester

Version

VoR (Version of Record)

Published in

American Journal of Transplantation

Volume

21

Issue

3

Pagination

1027-1038

Publisher

Wiley

issn

1600-6135

eissn

1600-6143

Acceptance date

10/08/2020

Copyright date

2020

Available date

09/09/2021

Language

en