title: A live imaging cell motility screen identifies prostaglandin E2 as a T cell stop signal antagonist.
abstract: The T cell migration stop signal is a central step in T cell activation and inflammation; however, its regulatory mechanisms remain largely unknown. Using a live-cell, imaging-based, high-throughput screen, we identified the PG, PGE(2), as a T cell stop signal antagonist. Src kinase inhibitors, microtubule inhibitors, and PGE(2) prevented the T cell stop signal, and impaired T cell-APC conjugation and T cell proliferation induced by primary human allogeneic dendritic cells. However, Src inhibition, but not PGE(2) or microtubule inhibition, impaired TCR-induced ZAP-70 signaling, demonstrating that T cell stop signal antagonists can function either upstream or downstream of proximal TCR signaling. Moreover, we found that PGE(2) abrogated TCR-induced activation of the small GTPase Rap1, suggesting that PGE(2) may modulate T cell adhesion and stopping through Rap1. These results identify a novel role for PGs in preventing T cell stop signals and limiting T cell activation induced by dendritic cells.
authors: Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA.
authors: Andrew J
authors: AJ
authors: Wiemer
authors: Subramanya
authors: S
authors: Hegde
authors: Jenny E
authors: JE
authors: Gumperz
authors: Anna
authors: A
authors: Huttenlocher
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology* / Q000378:metabolism; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D015232:Dinoprostone