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Nat Immunol. 2016 Sep;17(9):1093-101. doi: 10.1038/ni.3522. Epub 2016 Aug 1.

Affinity for self antigen selects Treg cells with distinct functional properties.

Author information

1
Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
2
Department of Nephrology, University Hospital Basel and University of Basel, Basel, Switzerland.
3
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
4
Molecular and Cellular Immunology/Immune Regulation, DFG-Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.
5
MRC Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
6
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea.
7
Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
8
Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany.
9
Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, Basel, Switzerland.
10
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.

Abstract

The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) Treg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)) Treg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4(+) Tconv cells into induced Treg cells (iTreg cells). Although Foxp3-deficient (Scurfy) mice lacked Treg cells, they contained Triple(hi)-like and Triple(lo)-like CD4(+) T cells zsuper> T cells infiltrated the skin, whereas Scurfy Triple(lo)CD4(+) T cells induced colitis and wasting disease. These findings indicate that the affinity of the T cell antigen receptor for self antigen drives the differentiation of Treg cells into distinct subsets with non-overlapping regulatory activities.

PMID:
27478940
PMCID:
PMC4994872
DOI:
10.1038/ni.3522
[Indexed for MEDLINE]
Free PMC Article

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