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Lymphostromal interactions in thymic development and function

Key Points

  • The thymus provides a specialized microenvironment for the efficient generation of T cells that bear the αβ form of the T-cell receptor.

  • The thymus is divided into cortical and medullary areas which are characterized by the presence of specialized thymic stromal cells, which are in intimate association with developing T-cell precursors.

  • Several studies have shown that the production of T cells in the thymus is dependent on signals from both epithelial cells and mesenchymal cells, the latter of which may also influence the development and growth of immature thymic epithelium.

  • Crosstalk mechanisms exist during thymus development in which immature thymocytes regulate the development of both cortical and medullary microenvironments.

  • Novel in vitro technologies involving thymic construction, together with gene targeting of defined thymic cell types, will be powerful tools with which to study mechanisms of thymic development and function.

Abstract

The generation of a peripheral T-cell pool is essential for normal immune system function. CD4+ and CD8+ T cells are produced most efficiently in the thymus, which provides a complexity of discrete cellular microenvironments. Specialized stromal cells, that make up such microenvironments, influence each stage in the maturation programme of immature T-cell precursors. Progress has recently been made in elucidating events that regulate the development of intrathymic microenvironments, as well as mechanisms of thymocyte differentiation. It is becoming increasingly clear that the generation and maintenance of thymic environments that are capable of supporting efficient T-cell development, requires complex interplay between lymphoid and stromal compartments of the thymus.

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Figure 1: Anatomical microenvironments in the adult thymus.
Figure 2: Model of molecular regulation during development of thymic epithelium.
Figure 3: Model of mesenchymal involvement in thymus development and function.
Figure 4: Experimental manipulation of the thymus in vitro.
Figure 5: Post-positive-selection expansion in the thymic medulla.

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Correspondence to Graham Anderson.

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DATABASE LINKS

LocusLink

AIRE

CD24

CD44

CD62L

CD69

Fgf10

FgfR2-IIIb

Foxn1

GM-CSF

hCRP

Hoxa3

IL-7

IL-7Rα

Notch-1

Pax-1

Pax-9

Qa-2

Rag-2

RelB

SAP

somatostatin

TR4

Glossary

PHARYNGEAL POUCH

A lateral diverticulum of the pharynx that meets a corresponding groove in the ectoderm.

ECTODERM

The uppermost layer of the three primary germ layers in the embryonic disc; it develops into the epidermis and epidermal tissues, the nervous system, the external sense organs and the mucous membranes that line the mouth and anus.

ENDODERM

The innermost of the three embryonic germ layers; it develops into the epithelium of the pharynx, respiratory tract, digestive tract, bladder and urethra.

STEM CELLS

A subset of cells which has a self-renewing capacity, and under appropriate conditions can give rise to a number of mature cell lineages.

MESENCHYME

Loosely organized, undifferentiated mesodermal cells.

NEURAL CREST

A group of embryonic cells that separate from the embryonic neural plate and migrate, giving rise to the spinal and autonomic ganglia, peripheral glia, chromaffin cells, melanocytes, some haematopoietic cells and mesenchyme.

EXTRACELLULAR MATRIX

Secreted products of many cell types which form an organized scaffold for cell support.

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Anderson, G., Jenkinson, E. Lymphostromal interactions in thymic development and function. Nat Rev Immunol 1, 31–40 (2001). https://doi.org/10.1038/35095500

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