title: Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance.
abstract: Although T helper (T(H)) cell-mediated immunity is required to effectively eliminate pathogens, unrestrained T(H) activity also contributes to tissue injury in many inflammatory and autoimmune diseases. We report here that the T(H) type 1 (T(H)1)-specific Tim-3 (T cell immunoglobulin domain, mucin domain) protein functions to inhibit aggressive T(H)1-mediated auto- and alloimmune responses. Tim-3 pathway blockade accelerated diabetes in nonobese diabetic mice and prevented acquisition of transplantation tolerance induced by costimulation blockade. These effects were mediated, at least in part, by dampening of the antigen-specific immunosuppressive function of CD4(+)CD25(+) regulatory T cell populations. Our data indicate that the Tim-3 pathway provides an important mechanism to down-regulate T(H)1-dependent immune responses and to facilitate the development of immunological tolerance.
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sánchez-Fueyo
authors.forename: Jane
authors.initials: J
authors.lastname: Tian
authors.forename: Dominic
authors.initials: D
authors.lastname: Picarella
authors.forename: Christoph
authors.initials: C
authors.lastname: Domenig
authors.forename: Xin Xiao
authors.initials: XX
authors.lastname: Zheng
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Sabatos
authors.forename: Natasha
authors.initials: N
authors.lastname: Manlongat
authors.forename: Orissa
authors.initials: O
authors.lastname: Bender
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: José-Carlos
authors.initials: JC
authors.lastname: Gutiérrez-Ramos
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Terry B
authors.initials: TB
authors.lastname: Strom
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D007107:Immune System / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D015375:Receptors, Interleukin-2; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D015375:Receptors, Interleukin-2; D011991:Receptors, Virus