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J Immunol. 2018 Dec 21. pii: ji1801026. doi: 10.4049/jimmunol.1801026. [Epub ahead of print]

Costimulation through TLR2 Drives Polyfunctional CD8+ T Cell Responses.

Author information

1
Department of Hematopoiesis, Sanquin Research-Amsterdam MC Landsteiner Laboratory, 1066 CX Amsterdam, the Netherlands.
2
Department of Hematopoiesis, Sanquin Research-Amsterdam MC Landsteiner Laboratory, 1066 CX Amsterdam, the Netherlands m.wolkers@sanquin.nl.

Abstract

Optimal T cell activation requires Ag recognition through the TCR, engagement of costimulatory molecules, and cytokines. T cells can also directly recognize danger signals through the expression of TLRs. Whether TLR ligands have the capacity to provide costimulatory signals and enhance Ag-driven T cell activation is not well understood. In this study, we show that TLR2 and TLR7 ligands potently lower the Ag threshold for cytokine production in T cells. To investigate how TLR triggering supports cytokine production, we adapted the protocol for flow cytometry-based fluorescence in situ hybridization to mouse T cells. The simultaneous detection of cytokine mRNA and protein with single-cell resolution revealed that TLR triggering primarily drives de novo mRNA transcription. Ifng mRNA stabilization only occurs when the TCR is engaged. TLR2-, but not TLR7-mediated costimulation, can enhance mRNA stability at low Ag levels. Importantly, TLR2 costimulation increases the percentage of polyfunctional T cells, a hallmark of potent T cell responses. In conclusion, TLR-mediated costimulation effectively potentiates T cell effector function to suboptimal Ag levels.

PMID:
30578304
DOI:
10.4049/jimmunol.1801026

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