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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2723-2731. Prepublished online as a Blood First Edition Paper on December 16, 2008; DOI 10.1182/blood-2008-06-162040. This Article Full Text Full Text (PDF) Supplemental Figure and Videos All Versions of this Article: blood-2008-06-162040v1 113/12/2723    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cuddihy, A. R. Articles by Crooks, G. M. Search for Related Content PubMed PubMed Citation Articles by Cuddihy, A. R. Articles by Crooks, G. M. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY VEGF-mediated cross-talk within the neonatal murine thymus Andrew R. Cuddihy1, Shundi Ge1, Judy Zhu1, Julie Jang1, Ann Chidgey2, Gavin Thurston3, Richard Boyd2, and Gay M. Crooks1,4 1 Division of Research Immunology and Bone Marrow Transplantation and Gene, Immune and Stem Cell Therapy (GISCT) Program, Childrens Hospital Los Angeles (CHLA), Los Angeles, CA; 2 Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Australia; 3 Regeneron Pharmaceuticals, Tarrytown, NY; and 4 Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles Although the mechanisms of cross-talk that regulate the hematopoietic and epithelial compartments of the thymus are well established, the interactions of these compartments with the thymic endothelium have been largely ignored. Current understanding of the thymic vasculature is based on studies of adult thymus. We show that the neonatal period represents a unique phase of thymic growth and differentiation, marked by endothelium that is organized as primitive, dense networks of capillaries dependent on vascular endothelial growth factor (VEGF). VEGF dependence in neonates is mediated by significantly higher levels of both VEGF production and endothelial VEGF receptor 2 (VEGF-R2) expression than in the adult thymus. VEGF is expressed locally in the neonatal thymus by immature, CD4–CD8– "double negative" (DN) thymocytes and thymic epithelium. Relative to adult thymus, the neonatal thymus has greater thymocyte proliferation, and a predominance of immature thymocytes and cortical thymic epithelial cells (cTECs). Inhibition of VEGF signaling during the neonatal period results in rapid loss of the dense capillaries in the thymus and a marked reduction in the number of thymocytes. These data demonstrate that, during the early postnatal period, VEGF mediates cross-talk between the thymocyte and endothelial compartments of the thymus. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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