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Gene-Deleted Mouse1
,
* Institut National de la Santé et de la Recherche Médicale Unité 548, Commissariat à l’Energie Atomique-Grenoble, Grenoble, France;
Developmental and Molecular Immunology, Department of Clinical and Biological Sciences, Center for Biomedicine, University of Basel, Basel, Switzerland; and
Institut National de la Santé et de la Recherche Médicale Unité 645, Université Franche-Comté, Établissement Français du Sang, Bourgogne Franche-Comté, Institut Fédératif de Recherche 133, Besançon, France
In pre-T
(pT) gene-deleted mice, the positively selectable CD4+CD8+ double-positive thymocyte pool is only 1% that in wild-type mice. Consequently, their peripheral T cell compartment is severely lymphopenic with a concomitant increase in proportion of CD25+FoxP3+ regulatory T cells. Using mixed bone marrow chimeras, where thymic output was 1% normal, the pT–/– peripheral T cell phenotype could be reproduced with normal cells. In the pT–/– thymus and peripheral lymphoid organs, FoxP3+CD4+ cells were enriched. Parabiosis experiments showed that many pT–/–CD4+ single-positive thymocytes represented recirculating peripheral T cells. Therefore, the enrichment of FoxP3+CD4+ single-positive thymocytes was not solely due to increased thymic production. Thus, the pT–/– mouse serves as a model system with which to study the consequences of chronic decreased thymic T cell production on the physiology of the peripheral T cell compartment.
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1 This work was carried out while N.B. was supported by a PhD scholarship from the Commissariat à l’Energie Atomique, France. A.G.R. is holder of the chair in Immunology endowed by R. Hoffman-La Roche (Basel, Switzerland).
2 N.B. and F.A. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Rhodri Ceredig, Department of Clinical and Biological Science, Developmental and Molecular Immunology, Center for Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland. E-mail address: Rod.Ceredig{at}unibas.ch
4 Abbreviations used in this paper: pT, pre-T; DN, double negative; DP, double positive; SP, single positive; TReg, regulatory T cell; WT, wild type; BM, bone marrow; LN, lymph node; PI, propidium iodide; i.c., intracytoplasmic; ISP, immature SP.
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