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Citation
Tags
HERO ID
6753432
Reference Type
Journal Article
Title
When Toll-like receptor and T-cell receptor signals collide: a mechanism for enhanced CD8 T-cell effector function
Author(s)
Geng, D; Zheng, L; Srivastava, R; Asprodites, N; Velasco-Gonzalez, C; Davila, E
Year
2010
Is Peer Reviewed?
Yes
Journal
Blood
ISSN:
0006-4971
EISSN:
1528-0020
Volume
116
Issue
18
Page Numbers
3494-3504
Language
English
PMID
20696947
DOI
10.1182/blood-2010-02-268169
Web of Science Id
WOS:000283853200019
Abstract
Emerging reports reveal that activating Toll-like receptor-2 (TLR2)-MyD88 signals in CD8 T lymphocytes enhances cytokine production and cytotoxicity; however, the signaling pathway remains undefined. In the present study, we examined the physiologic significance and molecular mechanisms involved in this process. We found that TLR2 engagement on T-cell receptor transgenic CD8 OT-1 T cells increased T-bet transcription factor levels consequently, augmenting effector transcript and protein levels both in vivo and in vitro. In contrast, TLR2 agonist did not costimulate TLR2(-/-)OT-1 or MyD88(-/-)OT-1 T cells. Elevated T-bet levels in TLR2-MyD88-activated T cells was a consequence of increased biosynthesis resulting from the enhanced activation of the mammalian target of the rapamycin (mTOR) pathway. Inhibiting mTOR, Akt, or protein kinase C in T cells abolished the costimulatory effects of the TLR2 agonist. In vivo, activating TLR2-MyD88 signals in T cells increased effector-molecule levels and enhanced the clearance of Listeria monocytogenes-Ova. These results help define a signaling pathway linking the TLR-MyD88 and mTOR pathway in an Akt- and protein kinase C-dependent manner. These results highlight a critical role for MyD88 signaling in T-cell activation and cytotoxicity. Furthermore, these findings offer the opportunity for improving the efficacy of vaccines and T cell-based immunotherapies by targeting TLR-MyD88 signaling within T cells.
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