TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation.
The newly identified TIM family of proteins is associated with regulation of T helper type 1 (T(H)1) and T(H)2 immune responses. TIM-1 is genetically linked to asthma and is a receptor for hepatitis A virus, but the endogenous ligand of TIM-1 is not known. Here we show that TIM-4, which is expressed by antigen-presenting cells, is the ligand for TIM-1. In vivo administration of either soluble TIM-1-immunoglobulin (TIM-1-Ig) fusion protein or TIM-4-Ig fusion protein resulted in hyperproliferation of T cells, and TIM-4-Ig costimulated T cell proliferation mediated by CD3 and CD28 in vitro. These data suggest that the TIM-1-TIM-4 interaction is involved in regulating T cell proliferation.
Meyers
Jennifer Hartt
JH
Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Chakravarti
Sumone
S
Schlesinger
David
D
Illes
Zsolt
Z
Waldner
Hanspeter
H
Umetsu
Sarah E
SE
Kenny
James
J
Zheng
Xin Xiao
XX
Umetsu
Dale T
DT
DeKruyff
Rosemarie H
RH
Strom
Terry B
TB
Kuchroo
Vijay K
VK
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007136:Immunoglobulins / Q000494:pharmacology; D008024:Ligands; D008565:Membrane Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D011485:Protein Binding; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D007136:Immunoglobulins; D008024:Ligands; D008565:Membrane Proteins; C500399:TIM-4 protein, mouse