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Published online before print February 16, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1006610

Received for publication October 3, 2006.
Revised November 29, 2006.
Accepted for publication January 10, 2007.

Article

Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17

Susumu Nakae ^*, Yoichiro Iwakura , Hajime Suto ^*, and Stephen J. Galli ^*@

*Department of Pathology, Stanford University School of Medicine, Stanford, California, USA; Atopy Research Center, Juntendo University, Tokyo, Japan; and Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan

^@ To whom correspondence should be addressed. E-mail: sgalli{at}stanford.edu.

	Abstract

Recent evidence from several groups indicates that IL-17-producing Th17 cells, rather than, as once was thought, IFN--producing Th1 cells, can represent the key effector cells in the induction/development of several autoimmune and allergic disorders. Although Th17 cells exhibit certain phenotypic and developmental differences from Th1 cells, the extent of the differences between these two T cell subsets is still not fully understood. We found that the expression profile of cell surface molecules on Th17 cells has more similarities to that of Th1 cells than Th2 cells. However, although certain Th1-lineage markers [i.e., IL-18 receptor , CXCR3, and T cell Ig domain, mucin-like domain-3 (TIM-3)], but not Th2-lineage markers (i.e., T1/ST2, TIM-1, and TIM-2), were expressed on Th17 cells, the intensity of expression was different between Th17 and Th1 cells. Moreover, the expression of CTLA-1, ICOS, programmed death ligand 1, CD153, Fas, and TNF-related activation-induced cytokine was greater on Th17 cells than on Th1 cells. We found that IL-23 or IL-17 can suppress Th1 cell differentiation in the presence of exogenous IL-12 in vitro. We also confirmed that IL-12 or IFN- can negatively regulate Th17 cell differentiation. However, these cytokines could not modulate such effects on T cell differentiation in the absence of APC.

Key Words: cytokines • T cells • flow cytometry

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