CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions.
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.
Dardalhon
Valerie
V
Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Schubart
Anna S
AS
Reddy
Jayagopala
J
Meyers
Jennifer Hartt
JH
Monney
Laurent
L
Sabatos
Catherine A
CA
Ahuja
Rakesh
R
Nguyen
Khuong
K
Freeman
Gordon J
GJ
Greenfield
Edward A
EA
Sobel
Raymond A
RA
Kuchroo
Vijay K
VK
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D011917:Rats, Inbred Lew; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D000098862:T Lineage-Specific Activation Antigen 1
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors