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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.

Type

Journal article

Journal

Development

Publication Date

04/2000

Volume

127

Pages

1583 - 1591

Keywords

Animals, Bone Marrow Cells, Bone Marrow Transplantation, CD3 Complex, Homeodomain Proteins, Mice, Mice, Transgenic, Phenotype, T-Lymphocyte Subsets, Thymus Gland