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Costimulation through TLR2 Drives Polyfunctional CD8⁺ T Cell Responses.

Fiamma Salerno¹, Julian J Freen-van Heeren¹, Aurelie Guislain¹

¹Department of Hematopoiesis, Sanquin Research-Amsterdam MC Landsteiner Laboratory, 1066 CX Amsterdam, the Netherlands.

Journal of Immunology (Baltimore, Md. : 1950)

|December 23, 2018

Summary

Toll-like receptor (TLR) ligands enhance T cell activation by lowering the antigen threshold for cytokine production. TLR2 and TLR7 ligands boost T cell responses, with TLR2 costimulation promoting polyfunctional T cells.

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Area of Science:

Immunology
Cellular Biology
Molecular Biology

Background:

Optimal T cell activation depends on T cell receptor (TCR) recognition, costimulatory signals, and cytokines.
T cells express Toll-like receptors (TLRs) that recognize danger signals, but their role in costimulation is unclear.

Purpose of the Study:

To investigate if TLR ligands can provide costimulatory signals and enhance antigen-driven T cell activation.
To determine the mechanisms by which TLR triggering supports T cell cytokine production.

Main Methods:

Adaptation of flow cytometry-based fluorescence in situ hybridization for mouse T cells.
Simultaneous detection of cytokine mRNA and protein at the single-cell level.

Main Results:

TLR2 and TLR7 ligands significantly lower the antigen threshold required for T cell cytokine production.
TLR triggering primarily enhances de novo mRNA transcription; mRNA stabilization requires TCR engagement.
TLR2 costimulation, unlike TLR7, enhances mRNA stability at low antigen levels and increases polyfunctional T cells.

Conclusions:

TLR-mediated costimulation potentiates T cell effector functions, even with suboptimal antigen levels.
TLR2 costimulation is particularly effective in enhancing T cell responses and promoting polyfunctional T cells.