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International Immunology Advance Access originally published online on August 30, 2006
International Immunology 2006 18(11):1509-1519; doi:10.1093/intimm/dxl084
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

An MHC-linked locus modulates thymic differentiation of CD4+CD25+Foxp3+ regulatory T lymphocytes

Julie Tellier1, Joost P. M. van Meerwijk1,2 and Paola Romagnoli1

1 Tolerance and Autoimmunity section, Centre de Physiopathologie de Toulouse Purpan, Institut National de la Santé et de la Recherche Médicale (INSERM) U563; University Paul Sabatier and IFR 30, Institut Claude de Preval, Toulouse, France
2 Institut Universitaire de France and Faculty of life-sciences (UFR-SVT), University Paul Sabatier, Toulouse, France

Correspondence to: J. P. M. van Meerwijk; E-mail: joost.van-meerwijk{at}toulouse.inserm.fr

CD4+CD25+Foxp3+ regulatory T lymphocytes are crucial for maintenance of immunological tolerance to self and innocuous non-self, are known to modulate immunity to tumors and infectious agents and can induce transplantation tolerance. Surprisingly, only a single genetic polymorphism is known to modulate regulatory T cell (Treg) development in the thymus, leading to a lethal autoimmune disorder. Here, we show that considerably different levels of Tregs are found in the thymi of distinct common laboratory mouse strains. We demonstrate that distinct levels of phenotypically and functionally identical Tregs develop with similar kinetics in the studied mice, that the responsible locus acts in a thymocyte-intrinsic manner and that levels of thymic Foxp3+ Tregs correlate to those found in the periphery. Using several congenic mouse strains, we mapped one of the at least two genetic loci capable of quantitatively modulating thymic Treg development to a ≤2.2 Mb region telomeric to the MHC. Our data indicate that polymorphic genes closely linked to the MHC locus substantially modulate differentiation of Tregs. Identification of responsible genes should help in understanding the mechanisms involved in commitment to the Treg lineage as well as selection of these cells in the thymus.

Keywords: T cells, thymus, tolerance

Transmitting editor: E. Vivier


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