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Cutting edge: TIGIT has T cell-intrinsic inhibitory functions
Nicole Joller1, Jason P Hafler, Boel Brynedal
1Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|January 5, 2011
Summary
Loss of the T cell Ig and ITIM domain (TIGIT) molecule in mice leads to overactive T cell responses and autoimmune disease. TIGIT directly inhibits T cell activation, independent of antigen-presenting cells.
Area of Science:
- Immunology
- Molecular Biology
- Autoimmunity
Background:
- Costimulatory molecules are crucial for T cell activation, with imbalances leading to infection or autoimmunity.
- The CD226/TIGIT pathway is a newly identified costimulatory pathway implicated in autoimmune diseases.
Purpose of the Study:
- To investigate the role of the coinhibitory molecule TIGIT in T cell regulation and autoimmunity.
- To determine if TIGIT directly inhibits T cell responses.
Main Methods:
- Generated TIGIT-deficient mice to study autoimmune susceptibility.
- Utilized an agonistic anti-TIGIT antibody to probe TIGIT function.
- Performed microarray analysis on T cells stimulated with anti-TIGIT antibody.
Main Results:
- Loss of TIGIT in mice resulted in hyperproliferative T cell responses and increased autoimmunity.
- TIGIT was shown to directly inhibit T cell responses, independent of antigen-presenting cells.
- Microarray data indicated TIGIT attenuates T cell receptor-driven activation signals.
Conclusions:
- TIGIT plays a direct inhibitory role in T cell activation.
- Dysregulation of the TIGIT pathway contributes to autoimmune disease development.
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