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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.

Titel:	Autoreactive T cell profiles are altered following allogeneic islet transplantation with alemtuzumab induction and re-emerging phenotype is associated with graft function.
Autor/in / Beteiligte Person:	Sabbah, S ; Liew, A ; Brooks, AM ; Kundu, R ; Reading, JL ; Flatt, A ; Counter, C ; Choudhary, P ; Forbes, S ; Rosenthal, MJ ; Rutter, MK ; Cairns, S ; Johnson, P ; Casey, J ; Peakman, M ; Shaw, JA ; Tree, TIM
Link:	Full Text Finder (Volltext)
Zeitschrift:	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jg. 21 (2021-03-01), Heft 3, S. 1027-1038
Veröffentlichung:	2023- : [New York] : Elsevier ; <i>Original Publication</i>: Copenhagen : Munksgaard International Publishers, 2001-, 2021
Medientyp:	academicJournal
ISSN:	1600-6143 (electronic)
DOI:	10.1111/ajt.16285
Schlagwort:	Alemtuzumab therapeutic use Graft Survival Humans Phenotype T-Lymphocytes Diabetes Mellitus, Type 1 Hematopoietic Stem Cell Transplantation Islets of Langerhans Transplantation
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Am J Transplant] 2021 Mar; Vol. 21 (3), pp. 1027-1038. <i>Date of Electronic Publication: </i>2020 Sep 19. MeSH Terms: Diabetes Mellitus, Type 1* ; Hematopoietic Stem Cell Transplantation* ; Islets of Langerhans Transplantation* ; Alemtuzumab / therapeutic use ; Graft Survival ; Humans ; Phenotype ; T-Lymphocytes References: Shapiro AMJ, Lakey JRT, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343(4):230-238. ; Brooks AM, Walker N, Aldibbiat A, et al. Attainment of metabolic goals in the integrated UK islet transplant program with locally isolated and transported preparations. Am J Transplant. 2013;13(12):3236-3243. ; Barton FB, Rickels MR, Alejandro R, et al. Improvement in outcomes of clinical islet transplantation: 1999-2010. Diabetes Care. 2012;35(7):1436-1445. ; Hering BJ, Bellin MD. TRANSPLANTATION sustained benefits of islet transplants for T1DM. Nat Rev Endocrinol. 2015;11(10):572-573. ; Qi M, Kinzer K, Danielson KK, et al. Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience. Acta Diabetol. 2014;51(5):833-843. ; Lablanche S, Borot S, Wojtusciszyn A, et al. Five-year metabolic, functional, and safety results of patients with type 1 diabetes transplanted with allogenic islets within the Swiss-French GRAGIL Network. Diabetes Care. 2015;38(9):1714-1722. ; Ryan EA, Paty BW, Senior PA, et al. Five-year follow-up after clinical islet transplantation. Diabetes. 2005;54(7):2060-2069. ; Brennan DC, Kopetskie HA, Sayre PH, et al. long-term follow-up of the edmonton protocol of islet transplantation in the United States. Am J Transplant. 2016;16(2):509-517. ; Fiorina P, Shapiro AM, Ricordi C, Secchi A. The clinical impact of islet transplantation. Am J Transplant. 2008;8(10):1990-1997. ; Keymeulen B, Gillard P, Mathieu C, et al. Correlation between beta cell mass and glycemic control in type 1 diabetic recipients of islet cell graft. Proc Natl Acad Sci USA. 2006;103(46):17444-17449. ; Emamaullee JA, Shapiro AM. Interventional strategies to prevent beta-cell apoptosis in islet transplantation. Diabetes. 2006;55(7):1907-1914. ; Carlsson PO, Palm F, Mattsson G. Low revascularization of experimentally transplanted human pancreatic islets. J Clin Endocrinol Metab. 2002;87(12):5418-5423. ; Bennet W, Groth CG, Larsson R, Nilsson B, Korsgren O. Isolated human islets trigger an instant blood mediated inflammatory reaction: implications for intraportal islet transplantation as a treatment for patients with type 1 diabetes. Ups J Med Sci. 2000;105(2):125-133. ; Brooks AM, Carter V, Liew A, et al. De novo donor-specific HLA antibodies are associated with rapid loss of graft function following islet transplantation in type 1 diabetes. Am J Transplant. 2015;15(12):3239-3246. ; Roep BO, Stobbe I, Duinkerken G, et al. Auto- and alloimmune reactivity to human islet allografts transplanted into type 1 diabetic patients. Diabetes. 1999;48(3):484-490. ; Gillard P, Ling Z, Mathieu C, et al. Comparison of sirolimus alone with sirolimus plus tacrolimus in type 1 diabetic recipients of cultured islet cell grafts. Transplantation. 2008;85(2):256-263. ; Piemonti L, Everly MJ, Maffi P, et al. Alloantibody and autoantibody monitoring predicts islet transplantation outcome in human type 1 diabetes. Diabetes. 2013;62(5):1656-1664. ; Hilbrands R, Huurman VA, Gillard P, et al. Differences in baseline lymphocyte counts and autoreactivity are associated with differences in outcome of islet cell transplantation in type 1 diabetic patients. Diabetes. 2009;58(10):2267-2276. ; Fiorina P, Vergani A, Petrelli A, et al. Metabolic and immunological features of the failing islet-transplanted patient. Diabetes Care. 2008;31(3):436-438. ; Nayak DK, Saravanan PB, Bansal S, Naziruddin B, Mohanakumar T. Autologous and allogenous antibodies in lung and islet cell transplantation. Front Immunol. 2016;7:650. ; Huurman VAL, Hilbrands R, Pinkse GGM, et al. Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation. PLoS One. 2008;3(6):e2435. ; Tyden G, Reinholt FP, Sundkvist G, Bolinder J. Recurrence of autoimmune diabetes mellitus in recipients of cadaveric pancreatic grafts. N Engl J Med. 1996;335(12):860-863. ; Monti P, Scirpoli M, Maffi P, et al. Islet transplantation in patients with autoimmune diabetes induces homeostatic cytokines that expand autoreactive memory T cells. J Clin Invest. 2008;118(5):1806-1814. ; Velthuis JH, Unger WW, Abreu JRF, et al. Simultaneous detection of circulating autoreactive CD8+ T-cells specific for different islet cell-associated epitopes using combinatorial MHC multimers. Diabetes. 2010;59(7):1721-1730. ; Workgroup on Hypoglycemia ADA. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005;28(5):1245-1249. ; Aldibbiat A, Huang GC, Zhao M, et al. Validation of islet transport from a geographically distant isolation center enabling equitable access and National Health Service funding of a clinical islet transplant program for England. Cell Transplant. 2012;21(1):382. ; Huang GC, Zhao M, Jones P, et al. The development of new density gradient media for purifying human islets and islet-quality assessments. Transplantation. 2004;77(1):143-145. ; Flatt AJS, Bennett D, Counter C, Brown AL, White SA, Shaw JAM. beta-Cell and renal transplantation options for diabetes. Diabet Med. 2020;37(4):580-592. ; Brooking H, Ananieva-Jordanova R, Arnold C, et al. A sensitive non-isotopic assay for GAD65 autoantibodies. Clin Chim Acta. 2003;331(1-2):55-59. ; Chen S, Willis J, Maclean C, et al. Sensitive non-isotopic assays for autoantibodies to IA-2 and to a combination of both IA-2 and GAD65. Clin Chim Acta. 2005;357(1):74-83. ; Powell M, Prentice L, Asawa T, et al. Glutamic acid decarboxylase autoantibody assay using 125I-labelled recombinant GAD65 produced in yeast. Clin Chim Acta. 1996;256(2):175-188. ; Arif S, Tree TI, Astill TP, et al. Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. J Clin Invest. 2004;113(3):451-463. ; Vantyghem M-C, Kerr-Conte J, Arnalsteen L, et al. Primary graft function, metabolic control, and graft survival after islet transplantation. Diabetes Care. 2009;32(8):1473-1478. ; Chujo D, Foucat E, Takita M, et al. Emergence of a broad repertoire of GAD65-specific T-cells in type 1 diabetes patients with graft dysfunction after allogeneic islet transplantation. Cell Transplant. 2012;21(12):2783-2795. ; Toso C, Edgar R, Pawlick R, et al. Effect of different induction strategies on effector, regulatory and memory lymphocyte sub-populations in clinical islet transplantation. Transpl Int. 2009;22(2):182-191. ; Ciancio G, Burke GW, Gaynor JJ, et al. A randomized trial of three renal transplant induction antibodies: early comparison of tacrolimus, mycophenolate mofetil, and steroid dosing, and newer immune-monitoring. Transplantation. 2005;80(4):457-465. ; Morales J, Bono MR, Fierro A, et al. Alemtuzumab induction in kidney transplantation: clinical results and impact on T-regulatory cells. Transplant Proc. 2008;40(9):3223-3228. ; Havari E, Turner MJ, Campos-Rivera J, et al. Impact of alemtuzumab treatment on the survival and function of human regulatory T cells in vitro. Immunology. 2014;141(1):123-131. ; Cox A, Thompson S, Jones J, et al. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol. 2005;35(11):3332-3342. ; Zhang X, Tao Y, Chopra M, et al. Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. J Immunol. 2013;191(12):5867-5874. ; Huurman VAL, Velthuis JHL, Hilbrands R, et al. Allograft-specific cytokine profiles associate with clinical outcome after islet cell transplantation. Am J Transplant. 2009;9(2):382-388. ; Arif S, Leete P, Nguyen VY, et al. Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes. Diabetes. 2014;63(11):3835-3845. ; Tree TIM, Lawson J, Edwards H, et al. Naturally arising human CD4 T-cells that recognize islet autoantigens and secrete interleukin-10 regulate proinflammatory T-cell responses via linked suppression. Diabetes. 2010;59(6):1451-1460. Grant Information: TCS/17/31 United Kingdom CSO_ Chief Scientist Office; 06/0003362 United Kingdom DUK_ Diabetes UK Contributed Indexing: Keywords: T cell biology; autoantibody; basic (laboratory) research/science; clinical research/practice; immunobiology; islet transplantation; islets of Langerhans; monitoring: immune Substance Nomenclature: 3A189DH42V (Alemtuzumab) Entry Date(s): Date Created: 20200901 Date Completed: 20210618 Latest Revision: 20230124 Update Code: 20231215

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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.