Abstract
Abstract Negative selection in the thymus ensures that only the functional and not the useless or harmful thymocytes will be exported into the circulation. The behavior of cells undergoing negative selection has been visualized only recently. However, the steady-state model used did not allow the precise reconstruction of the timeline of the events. To circumvent this drawback, we developed a model for visualizing synchronous negative selection following peptide injection, while avoiding the induction of non-specific cell death due to peripheral T cell activation. We observed that transgenic thymocytes slowed down significantly after the injection of their cognate peptide. This occurred very early, possibly within minutes of the injection. In addition, we established the time-course of cell activation and apoptosis induction in the system. Our data suggest that while stopping of the thymocytes is an event immediately downstream of the T cell receptor signaling, committing to death takes much longer time and most likely requires integration of multiple stimuli.
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