Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.

Foxp3(+) regulatory T cells (Treg) play a crucial role in regulating immune tolerance. The use of Treg to restore immune tolerance is considered an attractive novel approach to inhibit autoimmune disease, including type 1 diabetes (T1D), and to prevent rejection of organ transplants. In view of the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Weiting Du, Yueh-Wei Shen, Wen-Hui Lee, Ding Wang, Sachiko Paz, Fouad Kandeel, Chih-Pin Liu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4f633fe72c4746a9a6fff70f4b0d8717
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4f633fe72c4746a9a6fff70f4b0d8717
record_format	dspace
spelling	oai:doaj.org-article:4f633fe72c4746a9a6fff70f4b0d87172021-11-18T07:58:01ZFoxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.1932-620310.1371/journal.pone.0056209https://doaj.org/article/4f633fe72c4746a9a6fff70f4b0d87172013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23409157/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Foxp3(+) regulatory T cells (Treg) play a crucial role in regulating immune tolerance. The use of Treg to restore immune tolerance is considered an attractive novel approach to inhibit autoimmune disease, including type 1 diabetes (T1D), and to prevent rejection of organ transplants. In view of the goal of developing autologous Treg-based cell therapy for patients with long-term (>15 years) T1D, it will be necessary to expand a sufficient amount of functional Treg in vitro in order to study and compare Treg from T1D patients and healthy subjects. Our results have demonstrated that there is a comparable frequency of Treg in the peripheral blood lymphocytes (PBLs) of patients with long-term T1D relative to those in healthy subjects; however, Th1 cells, but not Th17 cells, were increased in the T1D patients. Further, more Treg in PBLs from T1D patients than from healthy subjects expressed the CD45RO(+) memory cell phenotype, suggesting they were antigen-experienced cells. After isolation, Treg from both T1D patients and healthy subjects were successfully expanded with high purity. Although there was no difference in Helios expression on Treg in PBLs, in vitro expansion led to fewer Helios-expressing Treg from T1D patients than healthy subjects. While more Th1-like Treg expressing IFN-γ or TNF-α were found in the PBLs of T1D patients than healthy controls, there was no such difference in the expanded Treg. Importantly, expanded Treg from both subject groups were able to suppress autologous or allogeneic CD8(+) effector T cells equally well. Our findings demonstrate that a large number of ex vivo expanded functional Treg can be obtained from long-term T1D patients, although fewer expanded Treg expressed a high level of Helios. Thus, based on the positive outcomes, these potent expanded Treg from diabetic human patients may be useful in treating T1D or preventing islet graft rejection.Weiting DuYueh-Wei ShenWen-Hui LeeDing WangSachiko PazFouad KandeelChih-Pin LiuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56209 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Weiting Du Yueh-Wei Shen Wen-Hui Lee Ding Wang Sachiko Paz Fouad Kandeel Chih-Pin Liu Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.
description	Foxp3(+) regulatory T cells (Treg) play a crucial role in regulating immune tolerance. The use of Treg to restore immune tolerance is considered an attractive novel approach to inhibit autoimmune disease, including type 1 diabetes (T1D), and to prevent rejection of organ transplants. In view of the goal of developing autologous Treg-based cell therapy for patients with long-term (>15 years) T1D, it will be necessary to expand a sufficient amount of functional Treg in vitro in order to study and compare Treg from T1D patients and healthy subjects. Our results have demonstrated that there is a comparable frequency of Treg in the peripheral blood lymphocytes (PBLs) of patients with long-term T1D relative to those in healthy subjects; however, Th1 cells, but not Th17 cells, were increased in the T1D patients. Further, more Treg in PBLs from T1D patients than from healthy subjects expressed the CD45RO(+) memory cell phenotype, suggesting they were antigen-experienced cells. After isolation, Treg from both T1D patients and healthy subjects were successfully expanded with high purity. Although there was no difference in Helios expression on Treg in PBLs, in vitro expansion led to fewer Helios-expressing Treg from T1D patients than healthy subjects. While more Th1-like Treg expressing IFN-γ or TNF-α were found in the PBLs of T1D patients than healthy controls, there was no such difference in the expanded Treg. Importantly, expanded Treg from both subject groups were able to suppress autologous or allogeneic CD8(+) effector T cells equally well. Our findings demonstrate that a large number of ex vivo expanded functional Treg can be obtained from long-term T1D patients, although fewer expanded Treg expressed a high level of Helios. Thus, based on the positive outcomes, these potent expanded Treg from diabetic human patients may be useful in treating T1D or preventing islet graft rejection.
format	article
author	Weiting Du Yueh-Wei Shen Wen-Hui Lee Ding Wang Sachiko Paz Fouad Kandeel Chih-Pin Liu
author_facet	Weiting Du Yueh-Wei Shen Wen-Hui Lee Ding Wang Sachiko Paz Fouad Kandeel Chih-Pin Liu
author_sort	Weiting Du
title	Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.
title_short	Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.
title_full	Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.
title_fullStr	Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.
title_full_unstemmed	Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.
title_sort	foxp3+ treg expanded from patients with established diabetes reduce helios expression while retaining normal function compared to healthy individuals.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4f633fe72c4746a9a6fff70f4b0d8717
work_keys_str_mv	AT weitingdu foxp3tregexpandedfrompatientswithestablisheddiabetesreduceheliosexpressionwhileretainingnormalfunctioncomparedtohealthyindividuals AT yuehweishen foxp3tregexpandedfrompatientswithestablisheddiabetesreduceheliosexpressionwhileretainingnormalfunctioncomparedtohealthyindividuals AT wenhuilee foxp3tregexpandedfrompatientswithestablisheddiabetesreduceheliosexpressionwhileretainingnormalfunctioncomparedtohealthyindividuals AT dingwang foxp3tregexpandedfrompatientswithestablisheddiabetesreduceheliosexpressionwhileretainingnormalfunctioncomparedtohealthyindividuals AT sachikopaz foxp3tregexpandedfrompatientswithestablisheddiabetesreduceheliosexpressionwhileretainingnormalfunctioncomparedtohealthyindividuals AT fouadkandeel foxp3tregexpandedfrompatientswithestablisheddiabetesreduceheliosexpressionwhileretainingnormalfunctioncomparedtohealthyindividuals AT chihpinliu foxp3tregexpandedfrompatientswithestablisheddiabetesreduceheliosexpressionwhileretainingnormalfunctioncomparedtohealthyindividuals
_version_	1718422727028637696

Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.

Ejemplares similares