Scientific article

Three-dimensional visualization of the mouse thymus organization in health and immunodeficiency

Published inThe Journal of immunology, vol. 190, no. 2, p. 586-596
Publication date2013

Lymphoid organs exhibit complex structures tightly related to their function. Surprisingly, although the thymic medulla constitutes a specialized microenvironment dedicated to the induction of T cell tolerance, its three-dimensional topology remains largely elusive because it has been studied mainly in two dimensions using thymic sections. To overcome this limitation, we have developed an automated method for full organ reconstruction in three dimensions, allowing visualization of intact mouse lymphoid organs from a collection of immunolabeled slices. We validated full organ reconstruction in three dimensions by reconstructing the well-characterized structure of skin-draining lymph nodes, before revisiting the complex and poorly described corticomedullary organization of the thymus. Wild-type thymi contain ~200 small medullae that are connected to or separated from a major medullary compartment. In contrast, thymi of immunodeficient Rag2(-/-) mice exhibit only ~20 small, unconnected medullary islets. Upon total body irradiation, medullary complexity was partially reduced and then recovered upon bone marrow transplantation. This intricate topology presents fractal properties, resulting in a considerable corticomedullary area. This feature ensures short distances between cortex and medulla, hence efficient thymocyte migration, as assessed by mathematical models. Remarkably, this junction is enriched, particularly in neonates, in medullary thymic epithelial cells expressing the autoimmune regulator. The emergence of a major medullary compartment is induced by CD4(+) thymocytes via CD80/86 and lymphotoxin-α signals. This comprehensive three-dimensional view of the medulla emphasizes a complex topology favoring efficient interactions between developing T cells and autoimmune regulator-positive medullary thymic epithelial cells, a key process for central tolerance induction.

  • Animals
  • Antigens, CD4/metabolism
  • Antigens, CD80/metabolism
  • Antigens, CD86/metabolism
  • Bone Marrow Transplantation
  • Epithelial Cells/metabolism
  • Imaging, Three-Dimensional/methods
  • Lymphoid Tissue/cytology/drug effects/pathology/radiation effects
  • Mice
  • Mice, Knockout
  • Thymocytes/metabolism
  • Thymus Gland/cytology/drug effects/pathology/radiation effects
Citation (ISO format)
IRLA, Magali et al. Three-dimensional visualization of the mouse thymus organization in health and immunodeficiency. In: The Journal of immunology, 2013, vol. 190, n° 2, p. 586–596. doi: 10.4049/jimmunol.1200119
Main files (1)
Article (Published version)
ISSN of the journal0022-1767

Technical informations

Creation07/16/2013 12:09:00 PM
First validation07/16/2013 12:09:00 PM
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