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Calcium oscillations regulate thymocyte motility during positive selection in the three-dimensional thymic
Nirav R Bhakta1, David Y Oh, Richard S Lewis
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature Immunology
|January 18, 2005
Summary
Developing T cells require specific calcium signals within the thymus for positive selection. This study reveals that increased calcium levels halt T cell movement, prolonging interactions crucial for T cell development.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- The thymic microenvironment and calcium signaling are vital for T cell positive selection.
- The precise nature and impact of calcium signals during T cell development remain unclear.
Purpose of the Study:
- To investigate the role of calcium signaling in regulating thymocyte motility during positive selection.
- To visualize real-time thymocyte behavior and signaling within a three-dimensional thymic environment.
Main Methods:
- Development of a novel thymic slice preparation.
- Utilized two-photon microscopy to observe thymocyte motility and intracellular calcium concentrations in real time.
Main Results:
- Naive thymocytes exhibited high motility at low intracellular calcium levels.
- During positive selection, thymocytes became immobile and displayed sustained calcium oscillations.
- Elevated intracellular calcium was both necessary and sufficient to arrest thymocyte motility.
Conclusions:
- Calcium signaling directly controls thymocyte motility, arresting movement during positive selection.
- This calcium-induced immobility extends thymocyte-stromal cell interactions, potentially enhancing positive selection signaling.
- The findings provide new insights into the mechanisms governing T cell development in the thymus.