An essential role for thymic mesenchyme in early T cell development

We show that the mesenchymal cells that surround the 12-d mouse embryo thym us are necessary for T cell differentiation. Thus, epithelial lobes with at tached mesenchyme generate all T cell populations in vitro, whereas lobes f rom which mesenchyme has been removed show poor lymphopoiesis with few cell s progressing beyond the CD4(-)CD8(-) stage of development. Interestingly, thymic mesenchyme is derived from neural crest cells, and extirpation of th e region of the neural crest involved results in impaired thymic developmen t and craniofacial abnormalities similar to the group of clinical defects f ound in the DiGeorge syndrome. Previous studies have suggested an inductive effect of mesenchyme on thymic epithelial morphogenesis. However, we have found that mesenchyme-derived f ibroblasts are still required for early T cell development in the presence of mature epithelial cells, and hence mesenchyme might have a direct role i n lymphopoiesis. We provide an anatomical basis for the role of mesenchyme by showing that mesenchymal cells migrate into the epithelial thymus to est ablish a network of fibroblasts and associated extracellular matrix. We pro pose that the latter might be important for T cell development through inte grin and/or cytokine interactions with immature thymocytes.