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T-cell development made simple


The thymus is the primary site of T-cell lymphopoiesis. However, the precise molecular interactions that enable the thymus to carry out this function are only recently being elucidated. Although several important molecular players have been identified, including soluble factors, extracellular matrix components, and integral membrane receptors and their ligands, the precise role of these molecules in thymocyte differentiation has yet to be fully characterized. In this regard, the advent of a simple and efficient culture system for the generation of T cells from stem cells, as discussed here, should greatly facilitate the study of T-cell development.

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Figure 1: Intrathymic T-cell development.
Figure 2: A simple schematic overview of Notch signalling.
Figure 3: T-cell development made simple: a schematic overview of stem cell–OP9-DL1 cell co-cultures, and potential applications/experimental approaches of this model system.


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I thank the Canadian Institutes for Health Research and the National Cancer Institute of Canada for their support. Apologies to all colleagues whose work was not cited owing to space constraints.

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delta-like 1

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(AIRE). A transcription factor that promotes the ectopic expression of peripheral tissue-restricted antigens by medullary epithelial cells of the thymus.


The deletion of self-reactive thymocytes in the thymus. Thymocytes that express T-cell receptors that strongly recognize self-peptide bound to self-MHC molecules undergo apoptosis in response to the signalling generated by high-affinity binding.


These mice are deficient in macrophage colony- stimulating factor (MCSF) owing to a naturally occurring recessive mutation, osteopetrosis (op), in the coding region of the MCSF gene.


The maturation of immature CD4+CD8+ precursor thymocytes induced by T-cell receptor (TCR) signals that result from binding to self-peptide–MHC ligands on thymic epithelial cells. This process selects thymocytes that express TCRs that can interact with self-MHC moelcules.


(siRNA). RNA interference (RNAi) is a phenomenon by which the expression of a specific gene is inhibited when a double-stranded complementary RNA (siRNA) is introduced into the organism.

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Zúñiga-Pflücker, J. T-cell development made simple. Nat Rev Immunol 4, 67–72 (2004).

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