Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease.
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.
Monney
Laurent
L
Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Sabatos
Catherine A
CA
Gaglia
Jason L
JL
Ryu
Akemi
A
Waldner
Hanspeter
H
Chernova
Tatyana
T
Manning
Stephen
S
Greenfield
Edward A
EA
Coyle
Anthony J
AJ
Sobel
Raymond A
RA
Freeman
Gordon J
GJ
Kuchroo
Vijay K
VK
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
D018845:CD11 Antigens; C448908:HAVCR2 protein, human; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D011991:Receptors, Virus