High TCR diversity ensures optimal function andhomeostasis of Foxp3 + regulatory Tcells

Lisa Föhse, Janine Suffner, Karsten Suhre, Benjamin Wahl, Cornelia Lindner, Chun Wei Lee, Susanne Schmitz, Jan D. Haas, Stella Lamprecht, Christian Koenecke, André Bleich, Günter J. Hämmerling, Bernard Malissen, Sebastian Suerbaum, Reinhold Förster, Immo Prinz

Research output: Contribution to journalArticle

58 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3101-3113
Number of pages13
JournalEuropean Journal of Immunology
Volume41
Issue number11
DOIs
Publication statusPublished - Nov 2011
Externally publishedYes

Fingerprint

Regulatory T-Lymphocytes
Autoantigens
Antigens
Adoptive Transfer
Graft vs Host Disease
Homeostasis
Food

Keywords

  • Experimental GvHD
  • Foxp3
  • High-throughput sequencing
  • TCR repertoire
  • Treg cells
  • Treg-homeostasis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

High TCR diversity ensures optimal function andhomeostasis of Foxp3 + regulatory Tcells. / 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: European Journal of Immunology, Vol. 41, No. 11, 11.2011, p. 3101-3113.

Research output: Contribution to journalArticle

Föhse, L, Suffner, J, Suhre, K, Wahl, B, Lindner, C, Lee, CW, 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 andhomeostasis of Foxp3 + regulatory Tcells', European Journal of Immunology, vol. 41, no. 11, pp. 3101-3113. https://doi.org/10.1002/eji.201141986
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. / High TCR diversity ensures optimal function andhomeostasis of Foxp3 + regulatory Tcells. In: European Journal of Immunology. 2011 ; Vol. 41, No. 11. pp. 3101-3113.
@article{03a9f8c64fe14e1d96d003461a566b51,
title = "High TCR diversity ensures optimal function andhomeostasis of Foxp3 + regulatory Tcells",
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 = "Experimental GvHD, Foxp3, High-throughput sequencing, TCR repertoire, Treg cells, Treg-homeostasis",
author = "Lisa F{\"o}hse and Janine Suffner and Karsten Suhre and Benjamin Wahl and Cornelia Lindner and Lee, {Chun Wei} 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",
year = "2011",
month = "11",
doi = "10.1002/eji.201141986",
language = "English",
volume = "41",
pages = "3101--3113",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "11",

}

TY - JOUR

T1 - High TCR diversity ensures optimal function andhomeostasis of Foxp3 + regulatory Tcells

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

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 - Experimental GvHD

KW - Foxp3

KW - High-throughput sequencing

KW - TCR repertoire

KW - Treg cells

KW - Treg-homeostasis

UR - http://www.scopus.com/inward/record.url?scp=80054953088&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054953088&partnerID=8YFLogxK

U2 - 10.1002/eji.201141986

DO - 10.1002/eji.201141986

M3 - Article

VL - 41

SP - 3101

EP - 3113

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 11

ER -