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J Immunol. 2011 Oct 1;187(7):3663-70. doi: 10.4049/jimmunol.1100103. Epub 2011 Sep 7.

A live imaging cell motility screen identifies prostaglandin E2 as a T cell stop signal antagonist.

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  • 1Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA.

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.

PMID:
21900181
[PubMed - indexed for MEDLINE]
PMCID:
PMC3178752
Free PMC Article

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