The Thymic Niche and Thymopoiesis

Abstract

The thymus, a bilobate gland located in the upper anterior thorax in higher vertebrates, is the major site of T‐lymphocyte production. This primary lymphoid organ composed of various nonlymphoid elements, referred to as the thymic stroma, governs the maturation and tolerance induction of haematopoietic precursors into immune‐competent nonautoreactive T cells. Whilst naturally involuting with age, the thymic stromal compartment remains dynamic in nature throughout life and retains the potential to regenerate.

Keywords: thymocyte; T lymphocyte; T‐cell receptor; differentiation; thymus

Figure 1.

Ultrastructure of the thymus. The thymic lobes are surrounded by the capsule (CAP) and are separated into a thymocyte‐rich cortex (C) and an epithelial cell‐rich medulla (M), separated by the corticomedullary junction (CMJ). The vasculature is mainly found in the medulla with its characteristic perivascular space (PVS).

Figure 2.

Overview of thymopoiesis. The precursors enter the thymus and then differentiate into distinct competent T‐cell populations. This process involves the sequential transition through various stages of maturation and intimate interaction with particular stromal elements composing the thymus. C, cortex; CAP, capsule; CLP, common lymphoid precursor, CMJ, corticomedullary junction; EDP, early double‐positive; ISP, immature single‐positive; L, lobule; LDP, late double‐positive; M, medulla; MHC, major histocompatibility complex; S, septae (trabeculae); SC, subcapsule; SMSP, semi‐mature single‐positive; T, T cell; TCR, T‐cell receptor. T‐cell differentiation pathway adapted from Boyd R and Hugo P (1991). Towards an integrated view of thymopoiesis. Immunology Today12: 71–79, with permission from Elsevier Science; the thymus ultrastructure was inspired from Van Ewijk W (1988) Cell surface topography of thymic microenvironments. Laboratory Investigation59: 579–590.

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References

Anderson MS, Venanzi ES, Klein L et al. (2002) Projection of an immunological self shadow within the thymus by the aire protein. Science 298: 1395–1401.

Aspinall R (2003) Age related changes in the function of T cells. Microscopy Research and Technique 62: 508–513.

Berzins SP, Boyd RL and Miller JFAP (1998) The role of the thymus and recent thymic migrants in the maintenance of the adult peripheral lymphocyte pool. Journal of Experimental Medicine 187: 1839–1848.

Bleul CC, Corbeaux T, Reuter A et al. (2006) Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 44: 992–996.

Bonasio R, Scimone ML, Schaerli P et al. (2006) Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nature Immunology 10: 1092–1100.

Derbinski J, Schulte A, Kyewski B and Klein L (2001) Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nature Immunology 2: 1032–1039.

Egawa T, Eberl G, Taniuchi I et al. (2005) Genetic evidence supporting selection of the Vα14i NKT cell lineage from double‐positive thymocyte precursors. Immunity 22: 705–716.

Gill J, Malin M, Hollander G and Boyd R (2004) Generation of a complete thymic microenvironment by MTS24+ thymic epithelial cells. Nature Immunology 3: 635–642.

Gillard GO and Farr AG (2006) Features of medullary thymic epithelium implicate postnatal development in maintaining epithelial heterogeneity and tissue‐restricted antigen expression. The Journal of Immunology 176: 5815–5824.

Gordon J, Wilson VA, Blair NF et al. (2004) Functional evidence for a single endodermal origin for the thymic epithelium. Nature Immunology 5: 546–553.

Gray D, Seach N, Ueono T et al. (2006) Developmental kinetics, turnover and stimulatory capacity of thymic epithelial cells. Blood 108: 3777–3785.

Itoi M, Kawamoto H, Katsura Y and Amagai T (2001) Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage. International Immunology 13: 1203–1211.

Jenkinson WE, Rossi SW, Jenkinson EJ and Anderson G (2005) Development of functional thymic epithelial cells occurs independently of lymphostromal interactions. Mechanism of Development 122: 1294–1299.

Lind EF, Prockop SE, Porritt HE and Petrie HT (2001) Mapping precursor movement through the postnatal thymus reveals specific microenvironments supporting defined stages of early lymphoid development. Journal of Experimental Medicine 194: 127–134.

Miller JFAP (2000) Discovering the origins of immunological competence. Annual Review of Immunology 17: 1–17.

Philp D, Pezzano M, Li Y et al. (1993) The binding, internalization, and release of thymocytes by thymic nurse cells. Cellular Immunology 148: 301–315.

Porritt HE, Rumfelt LL, Tabrizifard S et al. (2004) Heterogeneity among DN1 pro‐thymocytes reveals multiple progenitors with different capacities to generate T cell and non‐T cell lineage. Immunity 20: 735–745.

Radtke F, Wilson A, Stark G et al. (1999) Deficient T cell fate specification in mice with an induced inactivation of Notch 1. Immunity 10: 547–558.

Rossi FM, Corbel SY, Merzaban JS et al. (2005) Recruitment of adult thymic progenitors is regulated by P‐selectin and its ligand PSGL‐1. Nature Immunology 6: 626–634.

Rossi SW, Jenkinson WE, Anderson G and Jenkinson EJ (2006) Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium. Nature 441: 988–991.

Scimone L, Aifantis I, Apostolou I, von Boehmer H and von Andrian UH (2006) A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus. Proccedings of the National Academy of Sciences 103: 7006–7011.

Sutherland JS, Goldberg GL, Hammett MV et al. (2005) Activation of thymic regeneration in mice and humans following androgen blockade. The Journal of Immunology 175: 2741–2753.

Takahama Y (2006) Journey through the thymus: stromal guides for T‐cell development and selection. Nature Reviews Immunology 6: 127–135.

Taub DD and Longo DL (2005) Insights into thymic aging and regeneration. Immunological Reviews 205: 72–93.

Van den Brink MR, Alpdogan O and Boyd RL (2004) Strategies to enhance T‐cell reconstitution in immunocompromised patients. Nature Reviews Immunology 4: 856–867.

Van Ewijk W, Hollander G, Terhorst C and Wang B (2000) Stepwise development of thymic microenvironments in vivo is regulated by thymocyte subsets. Development 127: 1159–1583.

Visan I, Tan JB, Yuan JS et al. (2006) Regulation of T lymphopoiesis by Notch1 and Lunatic fringe‐mediated competition for intrathymic niches. Nature Immunology 6: 634–643.

Wu L and Shortman K (2005) Heterogeneity of thymic dendritic cells. Seminars in Immunology 17: 304–312.

Ye M and Graf T (2007) Early decisions in lymphoid development. Current Opinion in Immunology 19: 123–128.

Further Reading

Anderson G, Jenkinson WE, Jones T et al. (2006) Establishment and functioning of intrathymic microenvironments. Immunological Reviews 209: 10–27.

Gray DH, Ueno T, Chidgey AP et al. (2005) Controlling the thymic microenvironment. Current Opinions in Immunology 17: 137–143.

Hollander G, Gill J, Zuklys S et al. (2006) Cellular and molecular events during early thymus development. Immunological Reviews 209: 28–46.

Janeway CA, Travers P, Walport M and Capra JD (eds) (1999) The thymus and the development of T lymphocytes. In: Immunobiology. The Immune System in Health and Disease, 4th edn, pp. 227–260. New York: Elsevier.

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Chidgey, Ann, Boyd, Richard, and Hugo, Patrice(Sep 2007) The Thymic Niche and Thymopoiesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000526.pub2]