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Published on: May 30, 2013
CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions
Valerie Dardalhon1, Anna S Schubart, Jayagopala Reddy
1Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Insights
CD226 is a surface molecule specifically found on Th1 cells. Targeting CD226 reduces Th1 cell expansion and severity of Th1-mediated autoimmune diseases, suggesting its role in T cell activation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Differential expression of surface molecules on T helper cell subsets (Th1, Th2, Th0) is crucial for immune response regulation.
- Identifying specific markers can aid in controlling immune responses in vivo.
Purpose of the Study:
- To identify surface molecules differentially expressed on Th1 cells.
- To investigate the role of CD226 in T cell activation and Th1-mediated autoimmune diseases.
Main Methods:
- Utilized a panel of monoclonal antibodies (mAbs) to identify murine CD226 expression.
- Assessed CD226 expression on CD4 and CD8 T cells during activation and differentiation.
- Administered anti-CD226 in vivo to evaluate its effects on Th1 cell expansion, APCs, and experimental autoimmune encephalomyelitis (EAE).
Main Results:
- CD226 is specifically expressed on differentiated Th1 cells, not Th2 or Th0 cells.
- CD226 expression is up-regulated on activated CD4 cells and enhanced during Th1 differentiation, but down-regulated during Th2 polarization.
- In vivo anti-CD226 treatment reduced Th1 cell expansion, induced inhibitory APCs, and ameliorated EAE severity.
Conclusions:
- CD226 is a costimulatory molecule critical for Th1 cell activation and effector functions.
- Targeting CD226 offers a potential therapeutic strategy for Th1-mediated autoimmune conditions.
Abstract:
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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