title: Emerging Tim-3 functions in antimicrobial and tumor immunity.
abstract: T cell immunoglobulin-3 (Tim-3) has been identified as a marker of differentiated interferon-γ-producing CD4(+) T helper type 1 and CD8(+) T cytotoxic type 1 cells. The interaction of Tim-3 with its ligand, galectin-9 (Gal-9), induces cell death, and in vivo blockade of this interaction results in exacerbated autoimmunity and abrogation of tolerance in experimental models, establishing Tim-3 as a negative regulatory molecule. Recent studies have uncovered additional mechanisms by which Tim-3 negatively regulates T cell responses, such as promoting the development of CD8(+) T cell exhaustion and inducing expansion of myeloid-derived suppressor cells. In contrast to this inhibitory effect on T cells, Tim-3-Gal-9 interaction promotes macrophage clearance of intracellular pathogens. Here, we focus on the emerging role for Tim-3 in tumor and antimicrobial immunity.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kaori
authors.initials: K
authors.lastname: Sakuishi
authors.forename: Pushpa
authors.initials: P
authors.lastname: Jayaraman
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Behar
authors.forename: Ana C
authors.initials: AC
authors.lastname: Anderson
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis; D001424:Bacterial Infections / Q000276:immunology*; D037161:Galectins / Q000276:immunology* / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007165:Immunosuppression Therapy; D008262:Macrophage Activation; D008565:Membrane Proteins / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008565:Membrane Proteins