title: Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance.
abstract: T helper type 1 (T(H)1) immune responses are central in cell-mediated immunity, and a T(H)1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobulin (Ig) variable (V) domain of the full-length molecule. Fusion proteins (Tim-3-Ig) of both Tim-3 isoforms specifically bound CD4(+) T cells, indicating that a Tim-3 ligand is expressed on CD4(+) T cells. Administration of Tim-3-Ig to immunized mice caused hyperproliferation of T(H)1 cells and T(H)1 cytokine release. Tim-3-Ig also abrogated tolerance induction in T(H)1 cells, and Tim-3-deficient mice were refractory to the induction of high-dose tolerance. These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector T(H)1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance.
authors.affiliation: Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Sabatos
authors.forename: Sumone
authors.initials: S
authors.lastname: Chakravarti
authors.forename: Eugene
authors.initials: E
authors.lastname: Cha
authors.forename: Anna
authors.initials: A
authors.lastname: Schubart
authors.forename: Alberto
authors.initials: A
authors.lastname: Sánchez-Fueyo
authors.forename: Xin Xiao
authors.initials: XX
authors.lastname: Zheng
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Terry B
authors.initials: TB
authors.lastname: Strom
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
mesh_terms: D000906:Antibodies / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000276:immunology / Q000502:physiology; D000072597:Hepatitis A Virus Cellular Receptor 2; D007107:Immune System / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D008024:Ligands; D020033:Protein Isoforms; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D008024:Ligands; D020033:Protein Isoforms; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins