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PLoS By Category | Recent
PLoS Articles
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Immunology - Surgery
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Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8+ Suppressor T Cells
Published:
Wednesday, December 14, 2011
Author:
Yuming Yu et al.
by Yuming Yu, Jennifer R. Zitzner, Josetta Houlihan, Nancy Herrera, Luting Xu, Joshua Miller, James M. Mathew, Anat R. Tambur, Xunrong Luo
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 (?c) 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 ?c 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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