Porcine-Stimulated Human Tr1 Cells Showed Enhanced Suppression in Xenoantigen Stimulation Response

Type 1 regulatory T (Tr1) cells play a fundamental role in maintaining and inducing immune tolerance. Our preliminary study demonstrated that an interleukin- (IL-) 10-mediated pathway is a possible regulatory mechanism underlying the xenoantigen-specific human Treg enhanced suppressive capacity. Her...

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Autores principales:	Xiaoting Chen, Hongwen Ma, Lina Gong, Guang Yang, Xi Jin
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Computer applications to medicine. Medical informatics R858-859.7
Acceso en línea:	https://doaj.org/article/b78a25f61aad4877963a5ae25c76bbec
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spelling	oai:doaj.org-article:b78a25f61aad4877963a5ae25c76bbec2021-11-22T01:10:23ZPorcine-Stimulated Human Tr1 Cells Showed Enhanced Suppression in Xenoantigen Stimulation Response1748-671810.1155/2021/2725799https://doaj.org/article/b78a25f61aad4877963a5ae25c76bbec2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/2725799https://doaj.org/toc/1748-6718Type 1 regulatory T (Tr1) cells play a fundamental role in maintaining and inducing immune tolerance. Our preliminary study demonstrated that an interleukin- (IL-) 10-mediated pathway is a possible regulatory mechanism underlying the xenoantigen-specific human Treg enhanced suppressive capacity. Here, we developed a feasible protocol for expanding IL-10-induced xenoantigen-specific human Tr1 cells in vitro which would be more efficient in transplantation immunotherapy efficiency. In this study, xenoantigen-specific Tr1 cells are generated from human naive CD4+ T cells expanded for two subsequent xenoantigen-stimulation cycles with recombinant human IL-10. The phenotype and suppressive capacity of xenoantigen-stimulated Tr1 cells are assessed, and the mechanism of their suppression is studied. Tr1 cells can be induced by porcine xenoantigen stimulation combined with IL-10, IL-2, and IL-15, displaying an increased expression of CD49b, CTLA-4, and LAG-3 without expressing Foxp3 which also showed an effector memory Treg phenotype and expressed high levels of CD39. After xenoantigen stimulation, the IL-10 and IL-5 gene expression in Tr1 cells increased, secreting more IL-10, and xenoantigen-stimulated Tr1 cells changed their T cell receptor (TCR) Vβ repertoire, increasing the expression of TCR Vβ2, TCR Vβ9, and TCR Vβ13. In a pig to human mixed lymphocyte reaction (MLR), xenoantigen-stimulated Tr1 cells displayed enhanced suppressive capacity via CD39 in a dose-dependent manner. Moreover, IL-5 could affect the proliferation of xenoantigen-specific Tr1 cells, but not their phenotypes’ expression. This study provides a theory and feasible method for immune tolerance induction in clinical xenotransplantation.Xiaoting ChenHongwen MaLina GongGuang YangXi JinHindawi LimitedarticleComputer applications to medicine. Medical informaticsR858-859.7ENComputational and Mathematical Methods in Medicine, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Computer applications to medicine. Medical informatics R858-859.7
spellingShingle	Computer applications to medicine. Medical informatics R858-859.7 Xiaoting Chen Hongwen Ma Lina Gong Guang Yang Xi Jin Porcine-Stimulated Human Tr1 Cells Showed Enhanced Suppression in Xenoantigen Stimulation Response
description	Type 1 regulatory T (Tr1) cells play a fundamental role in maintaining and inducing immune tolerance. Our preliminary study demonstrated that an interleukin- (IL-) 10-mediated pathway is a possible regulatory mechanism underlying the xenoantigen-specific human Treg enhanced suppressive capacity. Here, we developed a feasible protocol for expanding IL-10-induced xenoantigen-specific human Tr1 cells in vitro which would be more efficient in transplantation immunotherapy efficiency. In this study, xenoantigen-specific Tr1 cells are generated from human naive CD4+ T cells expanded for two subsequent xenoantigen-stimulation cycles with recombinant human IL-10. The phenotype and suppressive capacity of xenoantigen-stimulated Tr1 cells are assessed, and the mechanism of their suppression is studied. Tr1 cells can be induced by porcine xenoantigen stimulation combined with IL-10, IL-2, and IL-15, displaying an increased expression of CD49b, CTLA-4, and LAG-3 without expressing Foxp3 which also showed an effector memory Treg phenotype and expressed high levels of CD39. After xenoantigen stimulation, the IL-10 and IL-5 gene expression in Tr1 cells increased, secreting more IL-10, and xenoantigen-stimulated Tr1 cells changed their T cell receptor (TCR) Vβ repertoire, increasing the expression of TCR Vβ2, TCR Vβ9, and TCR Vβ13. In a pig to human mixed lymphocyte reaction (MLR), xenoantigen-stimulated Tr1 cells displayed enhanced suppressive capacity via CD39 in a dose-dependent manner. Moreover, IL-5 could affect the proliferation of xenoantigen-specific Tr1 cells, but not their phenotypes’ expression. This study provides a theory and feasible method for immune tolerance induction in clinical xenotransplantation.
format	article
author	Xiaoting Chen Hongwen Ma Lina Gong Guang Yang Xi Jin
author_facet	Xiaoting Chen Hongwen Ma Lina Gong Guang Yang Xi Jin
author_sort	Xiaoting Chen
title	Porcine-Stimulated Human Tr1 Cells Showed Enhanced Suppression in Xenoantigen Stimulation Response
title_short	Porcine-Stimulated Human Tr1 Cells Showed Enhanced Suppression in Xenoantigen Stimulation Response
title_full	Porcine-Stimulated Human Tr1 Cells Showed Enhanced Suppression in Xenoantigen Stimulation Response
title_fullStr	Porcine-Stimulated Human Tr1 Cells Showed Enhanced Suppression in Xenoantigen Stimulation Response
title_full_unstemmed	Porcine-Stimulated Human Tr1 Cells Showed Enhanced Suppression in Xenoantigen Stimulation Response
title_sort	porcine-stimulated human tr1 cells showed enhanced suppression in xenoantigen stimulation response
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/b78a25f61aad4877963a5ae25c76bbec
work_keys_str_mv	AT xiaotingchen porcinestimulatedhumantr1cellsshowedenhancedsuppressioninxenoantigenstimulationresponse AT hongwenma porcinestimulatedhumantr1cellsshowedenhancedsuppressioninxenoantigenstimulationresponse AT linagong porcinestimulatedhumantr1cellsshowedenhancedsuppressioninxenoantigenstimulationresponse AT guangyang porcinestimulatedhumantr1cellsshowedenhancedsuppressioninxenoantigenstimulationresponse AT xijin porcinestimulatedhumantr1cellsshowedenhancedsuppressioninxenoantigenstimulationresponse
_version_	1718418363585134592

Porcine-Stimulated Human Tr1 Cells Showed Enhanced Suppression in Xenoantigen Stimulation Response

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