Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance.
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.
Sánchez-Fueyo
Alberto
A
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Tian
Jane
J
Picarella
Dominic
D
Domenig
Christoph
C
Zheng
Xin Xiao
XX
Sabatos
Catherine A
CA
Manlongat
Natasha
N
Bender
Orissa
O
Kamradt
Thomas
T
Kuchroo
Vijay K
VK
Gutiérrez-Ramos
José-Carlos
JC
Coyle
Anthony J
AJ
Strom
Terry B
TB
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*
C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D015375:Receptors, Interleukin-2; D011991:Receptors, Virus