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Epithelial Stem/Progenitor Cells in Thymus Organogenesis

  • Chapter
Adult Stem Cells

Abstract

The thymus provides a unique three-dimensional hematopoietic environment that is essential for the development of T (thymus-derived) lymphocytes. T-cell progenitors do not arise in the thymus itself, but migrate to the thymus from central hematopoietic organs such as the liver and bone marrow during fetal and adult life, respectively (1–3). Despite the fact that prethymic T lineage-committed progenitors have been identified (e.g., in fetal blood) (4),adult thymus-colonizing pro-T cells have remained elusive. Moreover, the molecular and cellular basis underlying thymus homing has not been resolved. Intrathymic stages of T-cell development have been studied in great detail both at the cellular and the molecular levels (reviewed in refs. 5–7). The intrathymic developmental sequence can be ordered into three major stages:

  1. 1.

    Growth factor-driven proliferation and protection from apoptosis of rare pro-T cells (growth factor expansion phase; reviewed in refs. 8 and 9).

  2. 2.

    Rearrangement of β, γ, and δ T-cell antigen receptor (TCR) genes, followed by thymocyte selection for further development based on the expression of productive TCR β-chains. This process, termed β-selection, depends on the assembly of the pre-TCR complex (reviewed in ref. 10). The β-selected thymocytes undergo massive proliferation and become CD4+CD8+, still immature, thymocytes.

  3. 3.

    Following TCR α-chain rearrangements, the pre-TCR is replaced by the αβTCR complex at the CD4+CD8+ stage. Cells that succeed to assemble a complete αβ-TCR can be selected based on TCR-MHC (major histocompatibility complex) interactions (αβ-selection). Thymocytes undergo further differentiation as CD4+CD8− (helper-type) or CD4−CD8+ (cytotoxic-type) singlepositive cells before they populate as MHC-restricted (positive selection) and self-tolerant (negative selection) antigen-reactive T cells the circulation and the peripheral lymphoid organs (reviewed in ref.5).

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  1. Hans-Reimer Rodewald
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Editors and Affiliations

  1. Hormones, Growth, and Development Program, Ottawa Health Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada

    Kursad Turksen

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Rodewald, HR. (2004). Epithelial Stem/Progenitor Cells in Thymus Organogenesis. In: Turksen, K. (eds) Adult Stem Cells. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-732-1_6

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  • DOI: https://doi.org/10.1007/978-1-59259-732-1_6

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-392-3

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