T-cell development is under the tight control of thymic microenvironments. Conversely, the integrity of thymic microenvironments depends on the physical presence of developing thymocytes, a phenomenon designated as 'thymic crosstalk'. We now show, using three types of immunodeficient mice, i.e. CD3(epsilon) transgenic mice, RAG(null) mice and RAG(null)-bone-marrow-transplanted CD3(epsilon) transgenic mice, that the control point in lymphoid development where triple negative (CD3(-),CD4(-),CD8(-)) thymocytes progress from CD44(+)CD25(-) towards CD44(-)CD25(+), influences the development of epithelial cells, critically inducing the extra, third dimension in the organization of the epithelial cells in the cortex. This tertiary configuration of the thymic epithelium is a typical feature for the thymus, enabling lymphostromal interaction during T-cell development. Crosstalk signals at this control point also induce the formation of thymic nurse cells. Moreover, our data indicate that establishment of a thymic cortex is a prerequisite for the development of the thymic medulla. Thus, differentiating thymocytes regulate the morphogenesis of thymic microenvironments in a stepwise fashion.

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Keywords Animals, Antigens, CD3/genetics/physiology, Bone Marrow Cells/physiology, Bone Marrow Transplantation, Homeodomain Proteins/genetics/physiology, Mice, Mice, Transgenic, Phenotype, Research Support, Non-U.S. Gov't, T-Lymphocyte Subsets/cytology/*physiology, Thymus Gland/cytology/*physiology
Persistent URL hdl.handle.net/1765/9292
Citation
van Ewijk, W., Hollander, G., Terhorst, C., & Wang, B.. (2000). Stepwise development of thymic microenvironments in vivo is regulated by thymocyte subsets. Development (Cambridge). Retrieved from http://hdl.handle.net/1765/9292