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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...

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Autores principales: Yu, Yuming, Zitzner, Jennifer R., Houlihan, Josetta, Herrera, Nancy, Xu, Luting, Miller, Joshua, Mathew, James M., Tambur, Anat R., Luo, Xunrong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
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.
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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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