The Journal of Experimental Medicine
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Published online 20 March 2000.
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© The Rockefeller University Press, 0022-1007/2000/3/1051/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 6, March 20, 2000 1051-1056

Brief Definitive Report

An Essential Role for Thymic Mesenchyme in Early T Cell Development

Ravinder K. Suniaraa, Eric J. Jenkinsona, and John J.T. Owena

a Department of Anatomy, Division of Immunity and Infection, Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom
Department of Anatomy, Division of Immunity and Infection, Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.44-121-414-681544-121-414-6821/2

suniarrk{at}bham.ac.uk

We show that the mesenchymal cells that surround the 12-d mouse embryo thymus are necessary for T cell differentiation. Thus, epithelial lobes with attached mesenchyme generate all T cell populations in vitro, whereas lobes from which mesenchyme has been removed show poor lymphopoiesis with few cells progressing beyond the CD4–CD8– stage of development. Interestingly, thymic mesenchyme is derived from neural crest cells, and extirpation of the region of the neural crest involved results in impaired thymic development and craniofacial abnormalities similar to the group of clinical defects found in the DiGeorge syndrome.

Previous studies have suggested an inductive effect of mesenchyme on thymic epithelial morphogenesis. However, we have found that mesenchyme-derived fibroblasts are still required for early T cell development in the presence of mature epithelial cells, and hence mesenchyme might have a direct role in lymphopoiesis. We provide an anatomical basis for the role of mesenchyme by showing that mesenchymal cells migrate into the epithelial thymus to establish a network of fibroblasts and associated extracellular matrix. We propose that the latter might be important for T cell development through integrin and/or cytokine interactions with immature thymocytes.

Key Words: stem cells • migration • fibroblasts • fibronectin • extracellular matrix

© 2000 The Rockefeller University Press


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