| First Author | Mariat C | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 3 | Pages | 1379-85 |
| PubMed ID | 19155484 | Mgi Jnum | J:144331 |
| Mgi Id | MGI:3830755 | Doi | 10.4049/jimmunol.182.3.1379 |
| Citation | Mariat C, et al. (2009) Tim-1 signaling substitutes for conventional signal 1 and requires costimulation to induce T cell proliferation. J Immunol 182(3):1379-85 |
| abstractText | Differentiation and clonal expansion of Ag-activated naive T cells play a pivotal role in the adaptive immune response. T cell Ig mucin (Tim) proteins influence the activation and differentiation of T cells. Tim-3 and Tim-2 clearly regulate Th1 and Th2 responses, respectively, but the precise influence of Tim-1 on T cell activation remains to be determined. We now show that Tim-1 stimulation in vivo and in vitro induces polyclonal activation of T cells despite absence of a conventional TCR-dependent signal 1. In this model, Tim-1-induced proliferation is dependent on strong signal 2 costimulation provided by mature dendritic cells. Ligation of Tim-1 upon CD4(+) T cells with an agonist anti-Tim-1 mAb elicits a rise in free cytosolic calcium, calcineurin-dependent nuclear translocation of NF-AT, and transcription of IL-2. Because Tim-4, the Tim-1 ligand, is expressed by mature dendritic cells, we propose that interaction between Tim-1(+) T cells and Tim-4(+) dendritic cells might ensure optimal stimulation of T cells, when TCR-derived signals originating within an inflamed environment are weak or waning. |
