Tim-2 regulates T helper type 2 responses and autoimmunity.
Identification of the T cell immunoglobulin mucin-domain containing (Tim) gene family introduced a new family of cell surface molecules that is involved in the regulation of immune responses. We previously demonstrated that Tim-3 is expressed on terminally differentiated T helper (Th)1 cells, and serves to regulate Th1 immune responses. Here, we describe the identification and function of Tim-2, a novel member of the Tim gene family. In contrast with Tim-3, we demonstrate that Tim-2 is expressed preferentially in differentiated Th2 cells. Blockade of the Tim-2/Tim-2 ligand interaction, by administration of soluble Tim-2 fusion protein (Tim-2 immunoglobulin [Ig]), results in T cell hyperproliferation and the production of Th2 cytokines. Administration of Tim-2 Ig during the induction phase reduces the severity of experimental autoimmune encephalomyelitis, a Th1-mediated autoimmune disease model of multiple sclerosis. We propose that Tim-2, an orthologue of human Tim-1, is critical for the regulation of Th2 responses during autoimmune inflammation.
Chakravarti
Sumone
S
Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Sabatos
Catherine A
CA
Xiao
Sheng
S
Illes
Zsolt
Z
Cha
Eugene K
EK
Sobel
Raymond A
RA
Zheng
Xin X
XX
Strom
Terry B
TB
Kuchroo
Vijay K
VK
D000818:Animals; D015551:Autoimmunity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D011991:Receptors, Virus / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D007074:Immunoglobulin G; D008565:Membrane Proteins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C442242:Timd2 protein, mouse