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

Autor: Lisa Föhse, Reinhold Förster, Chun Wei Lee, Christian Koenecke, Jan D. Haas, Karsten Suhre, André Bleich, Cornelia Lindner, Bernard Malissen, Sebastian Suerbaum, Immo Prinz, Benjamin Wahl, Günter J. Hämmerling, Janine Suffner, Stella Lamprecht, Susanne Schmitz
Přispěvatelé: Hannover Medical School [Hannover] (MHH), Deutsches Krebsforschungszentrum, Molekulare Immunologie, Molekulare immunologie, Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Faculty of Biology, Ludwig-Maximilians-Universität München (LMU), Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation (MHH), Institute for Medical Microbiology & Hospital Epidemiology - Hannover Medical School, Institute for Laboratory Animal Science - Hannover Medical School, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Inst. of Immunology, Helmholtz Zentrum München = German Research Center for Environmental Health, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Male
Adoptive cell transfer
Graft vs Host Disease
MESH: Flow Cytometry
Cell Separation
T-Lymphocytes
Regulatory
Mice
0302 clinical medicine
Immunology and Allergy
Homeostasis
MESH: Animals
MESH: High-Throughput Nucleotide Sequencing
0303 health sciences
medicine.diagnostic_test
biology
FOXP3
High-Throughput Nucleotide Sequencing
Forkhead Transcription Factors
MESH: Receptors
Antigen
T-Cell
hemic and immune systems
Experimental GvHD
Foxp3
High-throughput sequencing
TCR repertoire
Treg cells
Treg-homeostasis
Flow Cytometry
Adoptive Transfer
Self Tolerance
MESH: Homeostasis
MESH: Self Tolerance
[SDV.IMM]Life Sciences [q-bio]/Immunology
MESH: Mice
Transgenic
Transgene
Immunology
Receptors
Antigen
T-Cell
MESH: Graft vs Host Disease
Mice
Transgenic
chemical and pharmacologic phenomena
Major histocompatibility complex
MESH: Cell Separation
Flow cytometry
03 medical and health sciences
Antigen
MESH: Mice
Inbred C57BL
MESH: Forkhead Transcription Factors
medicine
Animals
MESH: Mice
030304 developmental biology
MESH: T-Lymphocytes
Regulatory
T-cell receptor
MESH: Male
Mice
Inbred C57BL
MESH: Adoptive Transfer
biology.protein
human activities
Function (biology)
030215 immunology
Zdroj: Eur. J. Immunol. 41, 3101-3113 (2011)
European Journal of Immunology
European Journal of Immunology, Wiley-VCH Verlag, 2011, 41 (11), pp.3101-13. ⟨10.1002/eji.201141986⟩
European Journal of Immunology, 2011, 41 (11), pp.3101-13. ⟨10.1002/eji.201141986⟩
ISSN: 0014-2980
1521-4141
DOI: 10.1002/eji.201141986⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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