Stepwise development of thymic microenvironments in vivo is regulated by thymocyte subsets
Van Ewijk W., Holländer G., Terhorst C., Wang B.
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. CD3ε transgenic mice, RAG(null) mice and RAG(null)-bone-marrow-transplanted CD3ε 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.