title: Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease.
abstract: Activation of naive CD4(+) T-helper cells results in the development of at least two distinct effector populations, Th1 and Th2 cells. Th1 cells produce cytokines (interferon (IFN)-gamma, interleukin (IL)-2, tumour-necrosis factor (TNF)-alpha and lymphotoxin) that are commonly associated with cell-mediated immune responses against intracellular pathogens, delayed-type hypersensitivity reactions, and induction of organ-specific autoimmune diseases. Th2 cells produce cytokines (IL-4, IL-10 and IL-13) that are crucial for control of extracellular helminthic infections and promote atopic and allergic diseases. Although much is known about the functions of these two subsets of T-helper cells, there are few known surface molecules that distinguish between them. We report here the identification and characterization of a transmembrane protein, Tim-3, which contains an immunoglobulin and a mucin-like domain and is expressed on differentiated Th1 cells. In vivo administration of antibody to Tim-3 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease, and increases the number and activation level of macrophages. Tim-3 may have an important role in the induction of autoimmune diseases by regulating macrophage activation and/or function.
authors.affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Monney
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Sabatos
authors.forename: Jason L
authors.initials: JL
authors.lastname: Gaglia
authors.forename: Akemi
authors.initials: A
authors.lastname: Ryu
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Waldner
authors.forename: Tatyana
authors.initials: T
authors.lastname: Chernova
authors.forename: Stephen
authors.initials: S
authors.lastname: Manning
authors.forename: Edward A
authors.initials: EA
authors.lastname: Greenfield
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Sobel
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018845:CD11 Antigens / Q000276:immunology; D003001:Cloning, Molecular; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D019891:Leukopoiesis; D008262:Macrophage Activation; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011991:Receptors, Virus; D018417:Th1 Cells / Q000276:immunology* / Q000637:transplantation
chemical_list: D018845:CD11 Antigens; C448908:HAVCR2 protein, human; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D011991:Receptors, Virus