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CD226 Is Specifically Expressed on the Surface of Th1 Cells and Regulates Their Expansion and Effector Functions¹

Valerie Dardalhon^2,*, Anna S. Schubart^2,*, Jayagopala Reddy^*, Jennifer Hartt Meyers^*, Laurent Monney^*, Catherine A. Sabatos^*, Rakesh Ahuja, Khuong Nguyen^3,, Gordon J. Freeman, Edward A. Greenfield^*,, Raymond A. Sobel^¶ and Vijay K. Kuchroo^4,*

^* Department of Neurology, Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115; Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720; Millennium Pharmaceuticals, Cambridge, MA 02139; and ^¶ Veterans Administration Health Care System, Palo Alto, and Department of Pathology, Stanford University School of Medicine, Stanford, CA 95305

Surface molecules that are differentially expressed on Th1 and Th2 cells may be useful in regulating specific immune responses in vivo. Using a panel of mAbs, we have identified murine CD226 as specifically expressed on the surface of differentiated Th1 cells but not Th2 or Th0 cells. Although CD226 is constitutively expressed on CD8 cells, it is up-regulated on CD4 cells upon activation. Th1 differentiation results in enhanced CD226 expression, whereas expression is down-regulated upon Th2 polarization. We demonstrate that CD226 is involved in the regulation of T cell activation; in vivo treatment with anti-CD226 results in significant reduction of Th1 cell expansion and in the induction of APCs that inhibit T cell activation. Furthermore, anti-CD226 treatment delays the onset and reduces the severity of a Th1-mediated autoimmune disease, experimental autoimmune encephalomyelitis. Our data suggest that CD226 is a costimulatory molecule that plays an important role in activation and effector functions of Th1 cells.

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				K. Shibuya, K. Shibata, S. Tahara-Hanaoka, and A. Shibuya Comment on "CD226 Is Specifically Expressed on the Surface of Th1 Cells and Regulates Their Expansion and Effector Functions" J. Immunol., April 1, 2006; 176(7): 3855 - 3855. [Full Text] [PDF]

				V. Dardalhon, A. S. Schubart, and V. K. Kuchroo Response to Comment on "CD226 Is Specifically Expressed on the Surface of Th1 Cells and Regulates Their Expansion and Effector Functions" J. Immunol., April 1, 2006; 176(7): 3856 - 3856. [Full Text] [PDF]