PT  - JOURNAL ARTICLE
AU  - van Ewijk, W.
AU  - Hollander, G.
AU  - Terhorst, C.
AU  - Wang, B.
TI  - Stepwise development of thymic microenvironments in vivo is regulated by thymocyte subsets
DP  - 2000 Apr 15
TA  - Development
PG  - 1583--1591
VI  - 127
IP  - 8
4099  - http://dev.biologists.org/content/127/8/1583.short
4100  - http://dev.biologists.org/content/127/8/1583.full
SO  - Development2000 Apr 15; 127
AB  - 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.