Thymic emigration revisited.
Conventional alphabeta 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 alphabeta 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 alphabeta 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 alphabeta 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.
McCaughtry
Tom M
TM
Center for Immunology, Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455.
Wilken
Matthew S
MS
Hogquist
Kristin A
KA
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D015704:CD4 Antigens; D049452:Green Fluorescent Proteins