Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8 Suppressor T CellsReportar como inadecuado




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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.



Autor: Yuming Yu, Jennifer R. Zitzner, Josetta Houlihan, Nancy Herrera, Luting Xu, Joshua Miller, James M. Mathew, Anat R. Tambur, Xunro

Fuente: http://plos.srce.hr/



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