Genetic control of thymic development of CD4+CD25+FoxP3+ regulatory T lymphocytes

Authors

  • Paola Romagnoli,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan (CPTP), IFR 30, Institut Claude de Preval, Toulouse, France
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  • Julie Tellier,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan (CPTP), IFR 30, Institut Claude de Preval, Toulouse, France
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  • Joost P. M. van Meerwijk

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan (CPTP), IFR 30, Institut Claude de Preval, Toulouse, France
    2. Institut Universitaire de France and Faculty of Life Sciences (UFR-SVT), University Toulouse III, Toulouse, France
    • INSERM U563, BP 3028, 31024 Toulouse Cedex 3, France, Fax: +33-562-74-45-58
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Abstract

Among the several mechanisms known to be involved in the establishment and maintenance of immunological tolerance, the activity of CD4+CD25+ regulatory T lymphocytes has recently incited most interest because of its critical role in inhibition of autoimmunity and anti-tumor immunity. Surprisingly, very little is known about potential genetic modulation of intrathymic regulatory T lymphocyte development. We show that distinct proportions of CD4+CD25+FoxP3+ regulatory T cells are found in thymi of common laboratory mouse strains. We demonstrate that distinct levels of phenotypically identical regulatory T cells develop with similar kinetics in the mice studied. Our experimental data on congenic mouse strains indicate that differences are not caused by the distinct MHC haplotypes of the inbred mouse strains. Moreover, the responsible loci act in a thymocyte-intrinsic manner, confirming the latter conclusion. We have not found any correlation between thymic and peripheral levels of regulatory T cells, consistent with known homeostatic expansion and/or retraction of the peripheral regulatory T cell pool. Our data indicate that polymorphic genes modulate differentiation of regulatory T cells. Identification of responsible genes may reveal novel clinical targets and still elusive regulatory T cell-specific markers. Importantly, these genes may also modulate susceptibility to autoimmune disease.

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