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High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells

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High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells. / Föhse, Lisa; Suffner, Janine; Suhre, Karsten; Wahl, Benjamin; Lindner, Cornelia; Lee, Chun-Wei; Schmitz, Susanne; Haas, Jan D; Lamprecht, Stella; Koenecke, Christian; Bleich, André; Hämmerling, Günter J; Malissen, Bernard; Suerbaum, Sebastian; Förster, Reinhold; Prinz, Immo.

in: EUR J IMMUNOL, Jahrgang 41, Nr. 11, 11.2011, S. 3101-13.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Föhse, L, Suffner, J, Suhre, K, Wahl, B, Lindner, C, Lee, C-W, Schmitz, S, Haas, JD, Lamprecht, S, Koenecke, C, Bleich, A, Hämmerling, GJ, Malissen, B, Suerbaum, S, Förster, R & Prinz, I 2011, 'High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells', EUR J IMMUNOL, Jg. 41, Nr. 11, S. 3101-13. https://doi.org/10.1002/eji.201141986

APA

Föhse, L., Suffner, J., Suhre, K., Wahl, B., Lindner, C., Lee, C-W., Schmitz, S., Haas, J. D., Lamprecht, S., Koenecke, C., Bleich, A., Hämmerling, G. J., Malissen, B., Suerbaum, S., Förster, R., & Prinz, I. (2011). High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells. EUR J IMMUNOL, 41(11), 3101-13. https://doi.org/10.1002/eji.201141986

Vancouver

Föhse L, Suffner J, Suhre K, Wahl B, Lindner C, Lee C-W et al. High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells. EUR J IMMUNOL. 2011 Nov;41(11):3101-13. https://doi.org/10.1002/eji.201141986

Bibtex

@article{45171b61b44b4c1f8480af91b5424e3f,
title = "High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells",
abstract = "Dominant tolerance to self-antigen requires the presence of sufficient numbers of CD4(+) Foxp3(+) Treg cells with matching antigen specificity. However, the size and role of TCR repertoire diversity for antigen-specific immuno-regulation through Treg cells is not clear. Here, we developed and applied a novel high-throughput (HT) TCR sequencing approach to analyze the TCR repertoire of Treg cells and revealed the importance of high diversity for Treg-cell homeostasis and function. We found that highly polyclonal Treg cells from WT mice vigorously expanded after adoptive transfer into non-lymphopenic TCR-transgenic recipients with low Treg-cell diversity. In that system, we identified specific Treg-cell TCR preferences in distinct anatomic locations such as the mesenteric LN indicating that Treg cells continuously compete for MHC class-II-presented self-, food-, or flora-antigen. Functionally, we showed that high TCR diversity was required for optimal suppressive function of Treg cells in experimental acute graft versus host disease (GvHD). In conclusion, we suggest that efficient immuno-regulation by Treg cells requires high TCR diversity. Thereby, continuous competition of peripheral Treg cells for limited self-antigen shapes an organ-optimized, yet highly diverse, local TCR repertoire.",
keywords = "Adoptive Transfer, Animals, Cell Separation, Flow Cytometry, Forkhead Transcription Factors/genetics, Graft vs Host Disease/immunology, High-Throughput Nucleotide Sequencing/methods, Homeostasis/genetics, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell/genetics, Self Tolerance/genetics, T-Lymphocytes, Regulatory/immunology",
author = "Lisa F{\"o}hse and Janine Suffner and Karsten Suhre and Benjamin Wahl and Cornelia Lindner and Chun-Wei Lee and Susanne Schmitz and Haas, {Jan D} and Stella Lamprecht and Christian Koenecke and Andr{\'e} Bleich and H{\"a}mmerling, {G{\"u}nter J} and Bernard Malissen and Sebastian Suerbaum and Reinhold F{\"o}rster and Immo Prinz",
note = "Copyright {\textcopyright} 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2011",
month = nov,
doi = "10.1002/eji.201141986",
language = "English",
volume = "41",
pages = "3101--13",
journal = "EUR J IMMUNOL",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag GmbH",
number = "11",

}

RIS

TY - JOUR

T1 - High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells

AU - Föhse, Lisa

AU - Suffner, Janine

AU - Suhre, Karsten

AU - Wahl, Benjamin

AU - Lindner, Cornelia

AU - Lee, Chun-Wei

AU - Schmitz, Susanne

AU - Haas, Jan D

AU - Lamprecht, Stella

AU - Koenecke, Christian

AU - Bleich, André

AU - Hämmerling, Günter J

AU - Malissen, Bernard

AU - Suerbaum, Sebastian

AU - Förster, Reinhold

AU - Prinz, Immo

N1 - Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2011/11

Y1 - 2011/11

N2 - Dominant tolerance to self-antigen requires the presence of sufficient numbers of CD4(+) Foxp3(+) Treg cells with matching antigen specificity. However, the size and role of TCR repertoire diversity for antigen-specific immuno-regulation through Treg cells is not clear. Here, we developed and applied a novel high-throughput (HT) TCR sequencing approach to analyze the TCR repertoire of Treg cells and revealed the importance of high diversity for Treg-cell homeostasis and function. We found that highly polyclonal Treg cells from WT mice vigorously expanded after adoptive transfer into non-lymphopenic TCR-transgenic recipients with low Treg-cell diversity. In that system, we identified specific Treg-cell TCR preferences in distinct anatomic locations such as the mesenteric LN indicating that Treg cells continuously compete for MHC class-II-presented self-, food-, or flora-antigen. Functionally, we showed that high TCR diversity was required for optimal suppressive function of Treg cells in experimental acute graft versus host disease (GvHD). In conclusion, we suggest that efficient immuno-regulation by Treg cells requires high TCR diversity. Thereby, continuous competition of peripheral Treg cells for limited self-antigen shapes an organ-optimized, yet highly diverse, local TCR repertoire.

AB - Dominant tolerance to self-antigen requires the presence of sufficient numbers of CD4(+) Foxp3(+) Treg cells with matching antigen specificity. However, the size and role of TCR repertoire diversity for antigen-specific immuno-regulation through Treg cells is not clear. Here, we developed and applied a novel high-throughput (HT) TCR sequencing approach to analyze the TCR repertoire of Treg cells and revealed the importance of high diversity for Treg-cell homeostasis and function. We found that highly polyclonal Treg cells from WT mice vigorously expanded after adoptive transfer into non-lymphopenic TCR-transgenic recipients with low Treg-cell diversity. In that system, we identified specific Treg-cell TCR preferences in distinct anatomic locations such as the mesenteric LN indicating that Treg cells continuously compete for MHC class-II-presented self-, food-, or flora-antigen. Functionally, we showed that high TCR diversity was required for optimal suppressive function of Treg cells in experimental acute graft versus host disease (GvHD). In conclusion, we suggest that efficient immuno-regulation by Treg cells requires high TCR diversity. Thereby, continuous competition of peripheral Treg cells for limited self-antigen shapes an organ-optimized, yet highly diverse, local TCR repertoire.

KW - Adoptive Transfer

KW - Animals

KW - Cell Separation

KW - Flow Cytometry

KW - Forkhead Transcription Factors/genetics

KW - Graft vs Host Disease/immunology

KW - High-Throughput Nucleotide Sequencing/methods

KW - Homeostasis/genetics

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Receptors, Antigen, T-Cell/genetics

KW - Self Tolerance/genetics

KW - T-Lymphocytes, Regulatory/immunology

U2 - 10.1002/eji.201141986

DO - 10.1002/eji.201141986

M3 - SCORING: Journal article

C2 - 21932448

VL - 41

SP - 3101

EP - 3113

JO - EUR J IMMUNOL

JF - EUR J IMMUNOL

SN - 0014-2980

IS - 11

ER -