Publications by authors named "Valerie J Brock"

Article Synopsis
  • * When T cell receptors are activated, NAADP is quickly produced, interacting with specific proteins that trigger the release of calcium from internal stores, leading to a rise in intracellular calcium levels.
  • * A new high-resolution imaging technique using two calcium indicators, along with a Python-based detection system, allows for the precise capture and analysis of these dynamic Ca microdomains in T cells and other cell types.
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Article Synopsis
  • * The study found that when these channels are absent, the formation of localized Ca signaling areas is impaired, affecting the speed and efficiency of T cell activation and their subsequent responses, like cytokine production and proliferation.
  • * Overall, purinergic signaling through P2X4 and P2X7 is essential for effective CD8 T cell function, highlighting the potential for targeting these pathways in future therapeutic strategies.
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Extracellular ATP activates the P2X7 receptor, leading to inflammasome activation and release of pro-inflammatory cytokines in monocytes. However, a detailed analysis of P2X7 receptor expression and function in the human T cell compartment has not been reported. Here, we used a P2X7-specific nanobody to assess cell membrane expression and function of P2X7 on peripheral T lymphocyte subsets.

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Initial T cell activation is triggered by the formation of highly dynamic, spatiotemporally restricted Ca microdomains. Purinergic signaling is known to be involved in Ca influx in T cells at later stages compared to the initial microdomain formation. Using a high-resolution Ca live-cell imaging system, we show that the two purinergic cation channels P2X4 and P2X7 not only are involved in the global Ca signals but also promote initial Ca microdomains tens of milliseconds after T cell stimulation.

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Live-cell Ca2+ fluorescence microscopy is a cornerstone of cellular signaling analysis and imaging. The demand for high spatial and temporal imaging resolution is, however, intrinsically linked to a low signal-to-noise ratio (SNR) of the acquired spatio-temporal image data, which impedes on the subsequent image analysis. Advanced deconvolution and image restoration algorithms can partly mitigate the corresponding problems but are usually defined only for images.

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