Details

Autor(en) / Beteiligte

• Yu, Yuming
• Zitzner, Jennifer R
• Houlihan, Josetta
• Herrera, Nancy
• Xu, Luting
• Miller, Joshua
• Mathew, James M
• Tambur, Anat R
• Luo, Xunrong
• Zissel, Gernot

Titel

Common gamma chain cytokines promote rapid in vitro expansion of allo-specific human CD8+ suppressor T cells

Ist Teil von

• PloS one, 2011-12, Vol.6 (12), p.e28948-e28948

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2011

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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.