Potentially harmful T cell precursors are removed from the conventional T cell pool by negative selection. This process can involve the induction of apoptosis, anergy, receptor editing or deviation into a regulatory T cell lineage. As such this process is essential for the health of an organism through its contribution to central and peripheral tolerance. While a great deal is known about the process, the precise mechanisms that regulate negative selection are not clear. Furthermore, the signals that distinguish the different forms of negative selection are not fully understood. Numerous models exist with the potential to address these questions in vitro and in vivo. This chapter describes methods of fetal thymic organ culture designed to analyze the signals that determine these unique cell fates.
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