NDLI: Human CCR4+ CCR6+ Th17 cells suppress autologous CD8+ T cell responses.

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Human CCR4+ CCR6+ Th17 cells suppress autologous CD8+ T cell responses.

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Human CCR4+ CCR6+ Th17 cells suppress autologous CD8+ T cell responses.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhao, Fei Wang, Xin Wei Wedemeyer, Heiner Korangy, Firouzeh Ormandy, Lars A. Hoechst, Bastian Greten, Tim F. Ylaya, Kris Gamrekelashvili, Jaba Voigtländer, Torsten Hewitt, Stephen M. Manns, Michael P.
Description	Country affiliation: United States Author Affiliation: Zhao F ( Gastrointestinal Malignancy Section, Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.)
Abstract	The role of Th17 cells in cancer patients remains unclear and controversial. In this study, we have analyzed the phenotype of in vitro primed Th17 cells and further characterized their function on the basis of CCR4 and CCR6 expression. We show a novel function for a subset of IL-17-secreting CD4(+) T cells, namely, CCR4(+)CCR6(+)Th17 cells. When cultured together, CCR4(+)CCR6(+)Th17 cells suppressed the lytic function, proliferation, and cytokine secretion of both Ag-specific and CD3/CD28/CD2-stimulated autologous CD8(+) T cells. In contrast, CCR4(-)CCR6(+) CD4(+) T cells, which also secrete IL-17, did not affect the CD8(+) T cells. Suppression of CD8(+) T cells by CCR4(+)CCR6(+)Th17 cells was partially dependent on TGF-ß, because neutralization of TGF-ß in cocultures reversed their suppressor function. In addition, we also found an increase in the frequency of CCR4(+)CCR6(+), but not CCR4(-)CCR6(+) Th17 cells in peripheral blood of hepatocellular carcinoma patients. Our study not only underlies the importance of analysis of subsets within Th17 cells to understand their function, but also suggests Th17 cells as yet another immune evasion mechanism in hepatocellular carcinoma. This has important implications when studying the mechanisms of carcinogenesis, as well as designing effective immunotherapy protocols for patients with cancer.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1102918
Journal	The Journal of Immunology
Issue Number	12
Volume Number	188
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cd8-positive T-lymphocytes Immunology Carcinoma, Hepatocellular Cell Communication Liver Neoplasms T-lymphocyte Subsets Th17 Cells Metabolism Coculture Techniques Cytokines Biosynthesis Enzyme-linked Immunosorbent Assay Flow Cytometry Immunohistochemistry Receptors, Ccr4 Receptors, Ccr6 Tumor Escape Research Support, N.i.h., Intramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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