Stepwise development of thymic microenvironments in vivo is regulated by thymocyte subsets.
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.
van Ewijk
W
W
Department of Immunology, Erasmus University Rotterdam, PO Box 1738, Rotterdam, The Netherlands. vanewijk@immu.fgg.eur.nl
Holländer
G
G
Terhorst
C
C
Wang
B
B
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*
D017252:CD3 Complex; D018398:Homeodomain Proteins; C064658:RAG-1 protein