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Curr Top Microbiol Immunol. 2011;350:1-15. doi: 10.1007/82_2010_84.

TIM-3 and its regulatory role in immune responses.

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Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA.


T cell immunoglobulin mucin-(TIM)-3 was first identified as a molecule specifically expressed on IFN-γ-secreting CD4(+) T helper 1 (Th1) and CD8(+) T cytotoxic (Tc1) cells in both mice and humans. TIM-3 acts as a negative regulator of Th1/Tc1 cell function by triggering cell death upon interaction with its ligand, galectin-9. This negative regulatory function of TIM-3 has now been expanded to include its involvement in establishing and/or maintaining a state of T cell dysfunction or "exhaustion" observed in chronic viral diseases. In addition, it is now appreciated that TIM-3 has other ligands and is expressed on other cell types, where it may function differently. Given that an increasing body of data support an important role for TIM-3 in both autoimmune and chronic inflammatory diseases in humans, deciphering the function of TIM-3 on different cell types during different immune conditions and how these can be regulated will be critical for harnessing the therapeutic potential of TIM-3 for the treatment of disease.

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