Thymic emigration revisited

J Exp Med. 2007 Oct 29;204(11):2513-20. doi: 10.1084/jem.20070601. Epub 2007 Oct 1.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Movement
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Humans
  • Immunologic Memory
  • Killer Cells, Natural / immunology
  • Mice
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • CD4 Antigens
  • Green Fluorescent Proteins