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