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Blood, 2 July 2009, Vol. 114, No. 1, pp. 105-108. Prepublished online as a Blood First Edition Paper on May 4, 2009; DOI 10.1182/blood-2009-03-211029. This Article Full Text Full Text (PDF) Supplemental Methods and Figure All Versions of this Article: blood-2009-03-211029v1 114/1/105    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 Google Scholar Articles by Poliani, P. L. Articles by Notarangelo, L. D. PubMed PubMed Citation Articles by Poliani, P. L. Articles by Notarangelo, L. D. Related Collections Immunobiology Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Brief report Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome Pietro Luigi Poliani1, Fabio Facchetti1, Maria Ravanini1, Andrew Richard Gennery2, Anna Villa3,4, Chaim M. Roifman5,*, and Luigi D. Notarangelo6,7,* 1 Department of Pathology, University of Brescia, Brescia, Italy; 2 Department of Paediatric Immunology, Newcastle upon Tyne Hospitals Foundation Trust, Newcastle upon Tyne, United Kingdom; 3 Telethon Institute for Gene Therapy–H San Raffaele, Milano, Italy; 4 Consiglio Nazionale delle Ricerche-Istituto Tecnologie Biomediche Segrate, Milano, Italy; 5 Hospital for Sick Children, Toronto, ON; and 6 Division of Immunology and 7 Manton Center for Orphan Diseases Research, Children's Hospital, Boston, MA Thymocytes and thymic epithelial cell (TEC) cross-talk is crucial to preserve thymic architecture and function, including maturation of TECs and dendritic cells, and induction of mechanisms of central tolerance. We have analyzed thymic maturation and organization in 9 infants with various genetic defects leading to complete or partial block in T-cell development. Profound abnormalities of TEC differentiation (with lack of AIRE expression) and severe reduction of thymic dendritic cells were identified in patients with T-negative severe combined immunodeficiency, reticular dysgenesis, and Omenn syndrome. The latter also showed virtual absence of thymic Foxp3+ T cells. In contrast, an IL2RG-R222C hypomorphic mutation permissive for T-cell development allowed for TEC maturation, AIRE expression, and Foxp3+ T cells. Our data provide evidence that severe defects of thymopoiesis impinge on TEC homeostasis and may affect deletional and nondeletional mechanisms of central tolerance, thus favoring immune dysreactive manifestations, as in Omenn syndrome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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