TIM-4 expressed on APCs induces T cell expansion and survival.
TIM (T cell, Ig, mucin) proteins can regulate T cell immune responses. Tim-4 mRNA is not expressed in T cells, but exclusively in APCs. Tim-4 is a ligand for Tim-1 and Tim-4.Ig fusion protein was shown to either inhibit or expand T cells. However, the molecular basis for such opposite effects was not defined. By generating mAbs, we show that expression of Tim-4 protein is restricted to CD11c(+) and CD11b(+) cells and is up-regulated upon activation. We show that Tim-4 specifically phosphorylates Tim-1 and induces T cell expansion by enhancing cell division and reducing apoptosis. Tim-4 also induces the phosphorylation of signaling molecules LAT, Akt, and ERK1/2 in T cells. Tim-4, expressed on APCs, is a costimulatory molecule that promotes T cell expansion and survival by cross-linking Tim-1 on T cells.
Rodriguez-Manzanet
Roselynn
R
Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Meyers
Jennifer Hartt
JH
Balasubramanian
Savithri
S
Slavik
Jacqueline
J
Kassam
Nasim
N
Dardalhon
Valerie
V
Greenfield
Edward A
EA
Anderson
Ana C
AC
Sobel
Raymond A
RA
Hafler
David A
DA
Strom
Terry B
TB
Kuchroo
Vijay K
VK
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D006224:Cricetinae; D005260:Female; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D051381:Rats; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D008565:Membrane Proteins; C500399:TIM-4 protein, mouse