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Human Th17 Cells Share Major Trafficking Receptors with Both Polarized Effector T Cells and FOXP3⁺ Regulatory T Cells¹

Hyung W. Lim^*, Jeeho Lee^*, Peter Hillsamer and Chang H. Kim^2,*

^* Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue Cancer Center, Bindley Bioscience Center, and Birck Nanotechnology Center, Purdue University, West Lafayette, IN 47907; and Sagamore Surgical Center, Lafayette, IN 47909

It is a question of interest whether Th17 cells express trafficking receptors unique to this Th cell lineage and migrate specifically to certain tissue sites. We found several Th17 cell subsets at different developing stages in a human secondary lymphoid organ (tonsils) and adult, but not in neonatal, blood. These Th17 cell subsets include a novel in vivo-stimulated tonsil IL17⁺ T cell subset detected without any artificial stimulation in vitro. We investigated in depth the trafficking receptor phenotype of the Th17 cell subsets in tonsils and adult blood. The developing Th17 cells in tonsils highly expressed both Th1- (CCR2, CXCR3, CCR5, and CXCR6) and Th2-associated (CCR4) trafficking receptors. Moreover, Th17 cells share major non-lymphoid tissue trafficking receptors, such as CCR4, CCR5, CCR6, CXCR3, and CXCR6, with FOXP3⁺ T regulatory cells. In addition, many Th17 cells express homeostatic chemokine receptors (CD62L, CCR6, CCR7, CXCR4, and CXCR5) implicated in T cell migration to and within lymphoid tissues. Expression of CCR6 and CCR4 by some Th17 cells is not a feature unique to Th17 cells but shared with FOXP3⁺ T cells. Interestingly, the IL17⁺IFN-⁺ Th17 cells have the features of both IL17^–IFN-⁺ Th1 and IL17⁺IFN-^– Th17 cells in expression of trafficking receptors. Taken together, our results revealed that Th17 cells are highly heterogeneous, in terms of trafficking receptors, and programmed to share major trafficking receptors with other T cell lineages. These findings have important implications in their distribution in the human body in relation to other regulatory T cell subsets.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health-National Institute of Allergy and Infectious Diseases Grant AI063064, American Heart Association, and Crohn’s and Colitis Foundation of America (to C.H.K.).

² Address correspondence and reprint requests to Dr. Chang Kim, Department of Comparative Pathobiology, 725 Harrison Street, Purdue University, West Lafayette, IN 47907. E-mail address: chkim{at}purdue.edu

³ Abbreviations used in this paper: PB, peripheral blood; Treg, regulatory T cell; 2° LT, secondary lymphoid tissues; CB, cord blood.

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