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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1974-1979. Prepublished online as a Blood First Edition Paper on November 10, 2005; DOI 10.1182/blood-2005-04-1495. This Article Full Text (PDF) All Versions of this Article: 2005-04-1495v1 107/5/1974    most recent Alert me when this article is cited Alert me if a correction is posted 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kumar, R. Articles by Snoeck, H.-W. Search for Related Content PubMed PubMed Citation Articles by Kumar, R. Articles by Snoeck, H.-W. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 12, 2005 Accepted October 12, 2005 Transforming growth factor-beta2 is involved in quantitative genetic variation in thymic involution Ritu Kumar, Jessica C Langer, and Hans-Willem Snoeck* Department for Cell and Gene Medicine, Mount Sinai School of Medicine, New York, NY, USA * Corresponding author; email: hans.snoeck{at}mssm.edu. The mechanisms regulating thymic involution are unclear. In inbred mouse strains the rate of thymic involution and the function of the hematopoietic stem cell (HSC) compartment are subject to quantitative genetic variation. We have shown previously that transforming growth factor-beta2 (TGF-2) is a genetically determined positive regulator of HSC. Here, we demonstrate that genetic variation in the rate of thymic involution correlates with genetic variation in the responsiveness of hematopoietic stem and progenitor cells to TGF-2. Corroborating these correlations, thymic cellularity and peripheral naive T cell frequency were higher in old Tgfb2+/- mice than in wt littermates. The frequency of early T cell precursors was increased in Tgfb2+/- mice, suggesting that TGF-2 affects the earliest stages of T cell development in old mice. Reciprocal transplantation experiments indicated that TGF-2 expressed both in the (micro)environment and in the hematopoietic system can accelerate thymic involution, however the age of the stem cells appeared irrelevant. Thus, although thymic involution is to largely determined by the aged environment, TGF-2 plays a major modulatory role that is subject to genetic variation and is possibly mediated through its regulatory effects on early hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. P. Zediak, I. Maillard, and A. Bhandoola Multiple prethymic defects underlie age-related loss of T progenitor competence Blood, August 15, 2007; 110(4): 1161 - 1167. [Abstract] [Full Text] [PDF]

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