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Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8(+) Suppressor T Cells
Human CD8(+) regulatory T cells, particularly the CD8(+)CD28(−) T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the cu...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237561/ https://www.ncbi.nlm.nih.gov/pubmed/22194954 http://dx.doi.org/10.1371/journal.pone.0028948 |
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author | Yu, Yuming Zitzner, Jennifer R. Houlihan, Josetta Herrera, Nancy Xu, Luting Miller, Joshua Mathew, James M. Tambur, Anat R. Luo, Xunrong |
author_facet | Yu, Yuming Zitzner, Jennifer R. Houlihan, Josetta Herrera, Nancy Xu, Luting Miller, Joshua Mathew, James M. Tambur, Anat R. Luo, Xunrong |
author_sort | Yu, Yuming |
collection | PubMed |
description | Human CD8(+) regulatory T cells, particularly the CD8(+)CD28(−) T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the current study, we develop a novel strategy that combines common gamma chain (γc) cytokines IL-2, IL-7 and IL-15 and donor antigen presenting cells (APCs) to stimulate full HLA-mismatched allogeneic human CD8(+) T cells which results in significant expansions of donor-specific CD8(+)CD28(−) T suppressor cells in vitro. The expanded CD8(+)CD28(−) T cells exhibit increased expressions of CTLA-4, FoxP3, and CD25, while down-regulate expressions of CD56, CD57, CD127, and perforin. Furthermore, these cells suppress proliferation of CD4(+) T cells in a contact-dependent and cytokine-independent manner. Interestingly, the specificity of suppression is restricted by the donor HLA class I antigens but promiscuous to HLA class II antigens, providing a potential mechanism for linked suppression. Taken together, our results demonstrate a novel role for common γc cytokines in combination with donor APCs in the expansion of donor-specific CD8(+)CD28(−) T suppressor cells, and represent a robust strategy for in vitro generation of such cells for adoptive cellular immunotherapy in transplantation. |
format | Online Article Text |
id | pubmed-3237561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32375612011-12-22 Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8(+) Suppressor T Cells Yu, Yuming Zitzner, Jennifer R. Houlihan, Josetta Herrera, Nancy Xu, Luting Miller, Joshua Mathew, James M. Tambur, Anat R. Luo, Xunrong PLoS One Research Article Human CD8(+) regulatory T cells, particularly the CD8(+)CD28(−) T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the current study, we develop a novel strategy that combines common gamma chain (γc) cytokines IL-2, IL-7 and IL-15 and donor antigen presenting cells (APCs) to stimulate full HLA-mismatched allogeneic human CD8(+) T cells which results in significant expansions of donor-specific CD8(+)CD28(−) T suppressor cells in vitro. The expanded CD8(+)CD28(−) T cells exhibit increased expressions of CTLA-4, FoxP3, and CD25, while down-regulate expressions of CD56, CD57, CD127, and perforin. Furthermore, these cells suppress proliferation of CD4(+) T cells in a contact-dependent and cytokine-independent manner. Interestingly, the specificity of suppression is restricted by the donor HLA class I antigens but promiscuous to HLA class II antigens, providing a potential mechanism for linked suppression. Taken together, our results demonstrate a novel role for common γc cytokines in combination with donor APCs in the expansion of donor-specific CD8(+)CD28(−) T suppressor cells, and represent a robust strategy for in vitro generation of such cells for adoptive cellular immunotherapy in transplantation. Public Library of Science 2011-12-14 /pmc/articles/PMC3237561/ /pubmed/22194954 http://dx.doi.org/10.1371/journal.pone.0028948 Text en Yu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yu, Yuming Zitzner, Jennifer R. Houlihan, Josetta Herrera, Nancy Xu, Luting Miller, Joshua Mathew, James M. Tambur, Anat R. Luo, Xunrong Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8(+) Suppressor T Cells |
title | Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8(+) Suppressor T Cells |
title_full | Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8(+) Suppressor T Cells |
title_fullStr | Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8(+) Suppressor T Cells |
title_full_unstemmed | Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8(+) Suppressor T Cells |
title_short | Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8(+) Suppressor T Cells |
title_sort | common gamma chain cytokines promote rapid in vitro expansion of allo-specific human cd8(+) suppressor t cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237561/ https://www.ncbi.nlm.nih.gov/pubmed/22194954 http://dx.doi.org/10.1371/journal.pone.0028948 |
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