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Proceedings of the National Academy of Sciences of the United States of America, (11 Aug 2008)
Cell death and differentiation 15 (2), 234-42 (Feb 2008)
Cell death and immunity Negative selection clearing out the bad apples from the Tcell repertoire
Nature Reviews Immunology 3 (5), 383-91 (May 2003)
Immunology Today 16 (6), 268 (1995)
The thymic medulla has always seemed a rather uncomplicated compartment, simply storing mature thymocytes until they are exported to the peripheral lymphoid organs. However, as discussed here by Roland Scollay and Dale Godfrey, a careful look at recent data suggests that events in the medulla may be more complex and protracted than previously thought.
The Journal of Experimental Medicine, jem-20070601 (01 Oct 2007)
Conventional {alpha}{beta} T cell precursors undergo positive selection in the thymic cortex. When this is successful, they migrate to the medulla and are exposed to tissue-specific antigens (TSA) for purposes of central tolerance, and they undergo maturation to become functionally responsive T cells. It is commonly understood that thymocytes spend up to 2 wk in the medulla undergoing these final maturation steps before emigrating to peripheral lymphoid tissues. In addition, emigration is thought to occur via a stochastic mechanism whereby some progenitors leave early and others leave late—a so-called "lucky dip" process. However, recent research has revealed that medullary thymocytes are a heterogeneous mix of naive {alpha}{beta} T cell precursors, memory T cells, natural killer T cells, and regulatory T cells. Given this, we revisited the question of how long it takes naive {alpha}{beta} T cell precursors to emigrate. We combined the following three approaches to study this question: BrdU labeling, intrathymic injection of a cellular tag, and RAG2p-GFP reporter mice. We established that, on average, naive {alpha}{beta} T cell precursors emigrate only 4–5 d after becoming single-positive (SP) thymocytes. Furthermore, emigration occurs via a strict "conveyor belt" mechanism, where the oldest thymocytes leave first.
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