The Journal of Experimental Medicine
Keystone Symposia 2010 Conferences
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Published online
doi:10.1084/jem.20070601
The Journal of Experimental Medicine, Vol. 204, No. 11, 2513-2520
The Rockefeller University Press, 0022-1007 $30.00
© McCaughtry et al.
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BRIEF DEFINITIVE REPORT

Thymic emigration revisited

Tom M. McCaughtry, Matthew S. Wilken, and Kristin A. Hogquist

Center for Immunology, Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455

CORRESPONDENCE Kristin A. Hogquist: hogqu001{at}umn.edu

Conventional {alpha}ß 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}ß 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}ß 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}ß 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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