Document Detail

Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45ro+CD25+CD127(low) regulatory T cells.
MedLine Citation:
PMID:  23280063     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Despite the high frequency of CD4+ T cells with a regulatory phenotype (CD25+CD127(low) FoxP3+) in the joints of patients with rheumatoid arthritis (RA), inflammation persists. One possible explanation is that human Treg cells are converted into proinflammatory interleukin-17 (IL-17)-producing cells by inflammatory mediators and thereby lose their suppressive function. The aim of this study was to investigate whether activated monocytes, which are potent producers of inflammatory cytokines and are abundantly present in the rheumatic joint, induce proinflammatory cytokine expression in human Treg cells and impair their regulatory function.
METHODS: The presence and phenotype of CD4+CD45RO+CD25+CD127(low) T cells (memory Treg cells) and CD14+ monocytes in the peripheral blood (PB) and synovial fluid (SF) of patients with RA were investigated by flow cytometry. Memory Treg cells obtained from healthy control subjects underwent fluorescence-activated cell sorting and then were cocultured with autologous activated monocytes and stimulated with anti-CD3 monoclonal antibodies. Intracellular cytokine expression, phenotype, and function of cells were determined by flow cytometry, enzyme-linked immunosorbent assay, and proliferation assays.
RESULTS: In patients with RA, the frequencies of CD4+CD45RO+CD25+CD127(low) Treg cells and activated CD14+ monocytes were higher in SF compared with PB. In vitro-activated monocytes induced an increase in the percentage of IL-17-positive, interferon-γ (IFNγ)-positive, and tumor necrosis factor α (TNFα)-positive Treg cells as well as IL-10-positive Treg cells. The observed increase in IL-17-positive and IFNγ-positive Treg cells was driven by monocyte-derived IL-1β, IL-6, and TNFα and was mediated by both CD14+CD16- and CD14+CD16+ monocyte subsets. Despite enhanced cytokine expression, cells maintained their CD25+FoxP3+CD39+ Treg cell phenotype and showed an enhanced capacity to suppress T cell proliferation and IL-17 production.
CONCLUSION: Treg cells exposed to a proinflammatory environment show increased cytokine expression as well as enhanced suppressive activity.
Gina J Walter; Hayley G Evans; Bina Menon; Nicola J Gullick; Bruce W Kirkham; Andrew P Cope; Frédéric Geissmann; Leonie S Taams
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-04-24     Revised Date:  2014-03-12    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  627-38     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
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MeSH Terms
Antigens, CD14 / metabolism
Antigens, CD4 / metabolism
Antigens, CD45 / metabolism
Arthritis, Rheumatoid / immunology*,  pathology
Cell Communication / immunology
Cells, Cultured
Coculture Techniques
Cytokines / metabolism*
GPI-Linked Proteins / metabolism
Immune Tolerance / immunology*
Immunologic Memory / immunology*
Interleukin-17 / metabolism
Interleukin-2 Receptor alpha Subunit / metabolism
Interleukin-6 / metabolism
Interleukin-7 Receptor alpha Subunit / metabolism
Middle Aged
Monocytes / cytology,  immunology*,  metabolism
Receptors, IgG / metabolism
Synovial Membrane / cytology,  immunology
T-Lymphocytes, Regulatory / cytology,  immunology*,  metabolism
Tumor Necrosis Factor-alpha / metabolism
Grant Support
19307//Arthritis Research UK; G0900867//Medical Research Council; //Arthritis Research UK
Reg. No./Substance:
0/Antigens, CD14; 0/Antigens, CD4; 0/Cytokines; 0/FCGR3B protein, human; 0/GPI-Linked Proteins; 0/IL17B protein, human; 0/IL6 protein, human; 0/Interleukin-17; 0/Interleukin-2 Receptor alpha Subunit; 0/Interleukin-6; 0/Interleukin-7 Receptor alpha Subunit; 0/Receptors, IgG; 0/Tumor Necrosis Factor-alpha; EC, CD45
Comment In:
Arthritis Rheum. 2013 Mar;65(3):552-4   [PMID:  23280009 ]

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