Submitted May 12, 2006
Accepted September 17, 2006
PDGFR
-expressing mesenchyme regulates thymus growth and the availability of intrathymic niches
William E Jenkinson, Simona W Rossi, Sonia M Parnell, Eric J Jenkinson, and Graham Anderson*
Institute for Biomedical Research, University of Birmingham Medical School, Birmingham, UK
* Corresponding author; email: g.anderson{at}bham.ac.uk.
The thymus provides a specialised site for the production of T-cells capable of recognising foreign antigens in the context of self-MHC molecules. During development, the thymus arises from an epithelial rudiment containing bipotent progenitors that differentiate into distinct cortical and medullary epithelial cells to regulate the maturation and selection of self-tolerant CD4+ and CD8+ T-cells. In addition to their differentiation, thymic epithelial cells undergo cellular expansion to ensure that sufficient intrathymic cellular niches are available to support the large number of immature thymocytes required to form a self-tolerant T-cell pool. Thus, intrathymic T-cell production is intimately linked to the formation and availability of niches within thymic microenvironments. Here, we show the increase in intrathymic niches caused by proliferation of epithelium in the developing thymus is temporally regulated, and correlates with the presence of a population of fetal thymic mesenchyme defined by Platelet Derived Growth Factor Receptor-alpha (PDGFR
) expression. Depletion of PDGFR+ mesenchyme from embryonic thymuses prior to their transplantation to ectopic sites results in the formation of functional, yet hypoplastic, thymic tissue. In summary, we highlight a specialised role for PDGFR+ fetal mesenchyme in the thymus by determining availability of thymic niches through the regulation of thymic epithelial proliferation.
