Costimulation through TLR2 drives polyfunctional CD8+ T cell responses

Salerno, F.; Freen, J. J.; Guislain, A.; Wolkers, M.

doi:10.1101/375840

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bioRxiv · 10.1101/375840

Costimulation through TLR2 drives polyfunctional CD8+ T cell responses

Salerno, F.·Freen, J. J.·Guislain, A.·Wolkers, M.

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Abstract

Optimal T cell activation requires antigen recognition through the T cell receptor (TCR), engagement of costimulatory molecules, and cytokines. T cells can also directly recognize danger signals through the expression of toll-like receptors (TLRs). Whether TLR ligands have the capacity to provide costimulatory signals and enhance antigen-driven T cell activation is not well understood. Here, we show that TLR2 and TLR7 ligands potently lower the antigen 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 (Flow-FISH) 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 antigen 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 antigen levels.

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Salerno, F., Freen, J. J., Guislain, A., Wolkers, M.. 2018-07-24. Costimulation through TLR2 drives polyfunctional CD8+ T cell responses. https://doi.org/10.1101/375840

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