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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901304v1 183/4/2261    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Lee, H. M. Articles by Hsieh, C.-S. PubMed PubMed Citation Articles by Lee, H. M. Articles by Hsieh, C.-S.

Rare Development of Foxp3⁺ Thymocytes in the CD4⁺CD8⁺ Subset¹

Department of Internal Medicine, Division of Rheumatology, Washington University, St. Louis, MO 63110

The CD4⁺CD8⁺ (double positive, DP) stage of thymic development is thought to be the earliest period that generates natural Foxp3⁺ regulatory T (Treg) cells important for the prevention of autoimmunity. However, we found that most Foxp3⁺ DP cells identified by routine flow cytometry represent doublets comprised of Foxp3^– DP and Foxp3⁺ CD4⁺CD8^– (CD4SP) cells. This was determined using analysis of flow cytometric height and width parameters, postsort contaminants, and thymocyte mixing studies. Temporal analysis of Treg cell development arising from bone marrow precursors in neonatal bone marrow chimeras suggested that Foxp3⁺ DP cells are not a major percentage of Foxp3⁺ thymocytes, and it supported the notion that most Treg cell development occurred at the immature HSA^high CD4SP stage. Thus, these data demonstrate that the frequency of Foxp3⁺ cells generated at the DP stage is much smaller than previously recognized, suggesting that additional thymocyte maturation may be required to facilitate efficient induction of Foxp3.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Heath Grant AI079187 and the Burroughs Wellcome Fund (to C.S.H.).

² Address correspondence and reprint requests to Dr. Chyi Hsieh, Department of Internal Medicine, Division of Rheumatology, Washington University, Box 8045, 660 South Euclid Avenue, St. Louis, MO 63110. E-mail address: chsieh{at}wustl.edu

³ Abbreviations used in this paper: Treg, regulatory T; CD4SP, CD4⁺CD8^– single positive; CD8SP, CD4^–CD8⁺ single positive; DP, CD4⁺CD8⁺ double positive; cTEC, cortical thymic epithelial cell; FSC, forward light scatter; mTEC, medullary thymic epithelial cell; SSC, side light scatter; HSA, heat-stable Ag (CD24); WT, wild type.

⁴ The online version of this article contains supplemental material.

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The JI 2009 183: 2201-2202. [Full Text]