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Immunity. 2016 May 17;44(5):1114-26. doi: 10.1016/j.immuni.2016.04.018.

Thymus-Derived Regulatory T Cells Are Positively Selected on Natural Self-Antigen through Cognate Interactions of High Functional Avidity.

Author information

1
Humboldt University of Berlin, Institute of Biology, 10115 Berlin, Germany; Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany.
2
Deutsches Rheuma-Forschungszentrum, a Leibniz Institute, 10117 Berlin, Germany.
3
Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany.
4
INRA, Unité de Virologie et Immunologie Moléculaire, 78352 Jouy en Josas, France.
5
Max Planck Institute of Infection Biology, 10117 Berlin, Germany.
6
Institute of Pathology/RCIS, Charité, Campus Benjamin Franklin, 12203 Berlin, Germany.
7
CPTP, INSERM UMR 1043 / CNRS UMR 5282, Université Toulouse III, 31024 Toulouse, France.
8
Institute for Molecular Medicine, Johannes Gutenberg University of Mainz, 55131 Mainz, Germany.
9
MRC Centre for Inflammation Research, University of Edinburgh, The Queens Medical Research Institute, Edinburgh, EH16 4TJ, UK.
10
Deutsches Rheuma-Forschungszentrum, a Leibniz Institute, 10117 Berlin, Germany; Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants Malades, Paris, France. Electronic address: simon.fillatreau@inserm.fr.

Abstract

Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4(+)Foxp3(-) T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen. The formation of these cells was impaired in mice lacking this self-antigen, while Tconv cell development was not negatively affected. Thymus-derived Treg cells were selected by self-antigens in a specific manner, while autoreactive Tconv cells were produced through degenerate recognition of distinct antigens. These distinct modes of development were associated with the expression of T cell receptor of higher functional avidity for self-antigen by Treg cells than Tconv cells, a difference subsequently essential for the control of autoimmunity. Our study documents how self-antigens define the repertoire of thymus-derived Treg cells to subsequently endow this cell type with the capacity to undermine autoimmune attack.

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PMID:
27192577
DOI:
10.1016/j.immuni.2016.04.018
[Indexed for MEDLINE]
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