Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes

Allogeneic islet transplantation has become an effective treatment option for severe Type 1 diabetes with intractable impaired awareness due to hypoglycemic events. Although current immunosuppressive protocols effectively prevent the acute rejection associated with initial T cell activation in recip...

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Autores principales:	Naoya Sato, Shigeru Marubashi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	islet transplantation tolerance induction apoptotic donor lymphocyte Medicine R
Acceso en línea:	https://doaj.org/article/e9218a7a69e449feaf66c1cfcf1f39c7
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spelling	oai:doaj.org-article:e9218a7a69e449feaf66c1cfcf1f39c72021-11-25T18:01:34ZInduction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes10.3390/jcm102253062077-0383https://doaj.org/article/e9218a7a69e449feaf66c1cfcf1f39c72021-11-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/22/5306https://doaj.org/toc/2077-0383Allogeneic islet transplantation has become an effective treatment option for severe Type 1 diabetes with intractable impaired awareness due to hypoglycemic events. Although current immunosuppressive protocols effectively prevent the acute rejection associated with initial T cell activation in recipients, chronic rejection has remained an obstacle for achieving long-term allogeneic islet engraftment. The development of donor-specific immune tolerance to the allograft is the ultimate goal given its potential ability to overcome chronic rejection and disregard the need for maintenance immunosuppression, which may be toxic to islet grafts. Recently, a breakthrough in tolerance induction during allogeneic islet transplantation using apoptotic donor lymphocytes (ADLs) in a non-human primate model had been reported. Several studies have suggested that the clonal depletion, anergy, and expansion of the antigen-specific regulatory immune network are the mechanisms for donor-specific tolerance with ADLs, which act synergistically to induce robust transplant tolerance. This achievement represents a huge step forward toward the clinical application of immune tolerance induction. We herein summarize the reported operational induction therapies in islet transplantation using the ADLs. Moreover, a few obstacles for the engraftment of transplanted islets, such as islet immunogenicity and instant blood-mediated response, which need to be resolved in the future, are also discussed.Naoya SatoShigeru MarubashiMDPI AGarticleislet transplantationtolerance inductionapoptotic donor lymphocyteMedicineRENJournal of Clinical Medicine, Vol 10, Iss 5306, p 5306 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	islet transplantation tolerance induction apoptotic donor lymphocyte Medicine R
spellingShingle	islet transplantation tolerance induction apoptotic donor lymphocyte Medicine R Naoya Sato Shigeru Marubashi Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes
description	Allogeneic islet transplantation has become an effective treatment option for severe Type 1 diabetes with intractable impaired awareness due to hypoglycemic events. Although current immunosuppressive protocols effectively prevent the acute rejection associated with initial T cell activation in recipients, chronic rejection has remained an obstacle for achieving long-term allogeneic islet engraftment. The development of donor-specific immune tolerance to the allograft is the ultimate goal given its potential ability to overcome chronic rejection and disregard the need for maintenance immunosuppression, which may be toxic to islet grafts. Recently, a breakthrough in tolerance induction during allogeneic islet transplantation using apoptotic donor lymphocytes (ADLs) in a non-human primate model had been reported. Several studies have suggested that the clonal depletion, anergy, and expansion of the antigen-specific regulatory immune network are the mechanisms for donor-specific tolerance with ADLs, which act synergistically to induce robust transplant tolerance. This achievement represents a huge step forward toward the clinical application of immune tolerance induction. We herein summarize the reported operational induction therapies in islet transplantation using the ADLs. Moreover, a few obstacles for the engraftment of transplanted islets, such as islet immunogenicity and instant blood-mediated response, which need to be resolved in the future, are also discussed.
format	article
author	Naoya Sato Shigeru Marubashi
author_facet	Naoya Sato Shigeru Marubashi
author_sort	Naoya Sato
title	Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes
title_short	Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes
title_full	Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes
title_fullStr	Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes
title_full_unstemmed	Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes
title_sort	induction of immune tolerance in islet transplantation using apoptotic donor leukocytes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e9218a7a69e449feaf66c1cfcf1f39c7
work_keys_str_mv	AT naoyasato inductionofimmunetoleranceinislettransplantationusingapoptoticdonorleukocytes AT shigerumarubashi inductionofimmunetoleranceinislettransplantationusingapoptoticdonorleukocytes
_version_	1718411776017563648

Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes

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