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The GITR-GITRL interaction: co-stimulation or contrasuppression of regulatory activity?
Ethan M Shevach1, Geoffrey L Stephens
1Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. eshevach@niaid.nih.gov
Nature Reviews. Immunology
|July 27, 2006
Summary
Stimulating glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) on T cells can boost anti-tumor immunity but also worsen autoimmune conditions. This study proposes GITR signaling co-stimulates both T cell responses and regulatory T cell suppression.
Area of Science:
- Immunology
- Cellular Biology
- Cancer Research
Background:
- Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) stimulation enhances anti-tumor and anti-viral immunity.
- GITR stimulation is also implicated in exacerbating autoimmune diseases.
- Current understanding suggests GITR's effects stem from suppressing CD4+ CD25+ regulatory T (Treg) cells.
Approach:
- Propose a novel model for GITR function.
- Investigate the dual role of GITR-GITR ligand interactions.
- Analyze co-stimulatory effects on T cells and Treg cells.
Key Points:
- GITR signaling impacts both effector T cells and regulatory T cells.
- GITR-ligand interactions provide co-stimulatory signals.
- This co-stimulation affects both immune activation and suppression.
Conclusions:
- GITR signaling has a more complex role than previously understood.
- GITR co-stimulates responder T cell functions.
- GITR also co-stimulates the suppressive functions of regulatory T cells.
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