| First Author | Rodriguez-Manzanet R | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 7 | Pages | 4706-13 |
| PubMed ID | 18354194 | Mgi Jnum | J:133386 |
| Mgi Id | MGI:3778355 | Doi | 10.4049/jimmunol.180.7.4706 |
| Citation | Rodriguez-Manzanet R, et al. (2008) TIM-4 Expressed on APCs Induces T Cell Expansion and Survival. J Immunol 180(7):4706-4713 |
| abstractText | 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. |
