NDLI: Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45ro+CD25+CD127(low) regulatory T cells.

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Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45ro+CD25+CD127(low) regulatory T cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Walter, Gina J. Evans, Hayley G. Menon, Bina Gullick, Nicola J. Kirkham, Bruce W. Cope, Andrew P. Geissmann, Frédéric Taams, Leonie S.
Description	Country affiliation: United kingdom Author Affiliation: Walter GJ ( King's College London, London, UK.)
Abstract	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-Î³ (IFNÎ³)-positive, and tumor necrosis factor (TNF )-positive Treg cells as well as IL-10-positive Treg cells. The observed increase in IL-17-positive and IFNÎ³-positive Treg cells was driven by monocyte-derived IL-1ß, IL-6, and TNF 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.
File Format	HTM / HTML
ISSN	00043591
e-ISSN	15290131
DOI	10.1002/art.37832
Journal	Arthritis & Rheumatism
Issue Number	3
Volume Number	65
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2013-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Cd45 Research Support, Non-u.s. Gov't Antigens, Cd4 Coculture Techniques Cytology Interleukin-6 Receptors, Igg Immunology Interleukin-7 Receptor Alpha Subunit Gpi-linked Proteins Synovial Membrane Interleukin-17 Interleukin-2 Receptor Alpha Subunit Cytokines Antigens, Cd14 Cells, Cultured Immune Tolerance Cell Communication Immunophenotyping T-lymphocytes, Regulatory Metabolism Tumor Necrosis Factor-alpha Arthritis, Rheumatoid Pathology Monocytes Immunologic Memory Discipline Rheumatic Diseases
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Pharmacology (medical) Rheumatology

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Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127(low) Treg Cells in Patients With Chronic Rheumatoid Arthritis.

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Tryptophan deprivation induces inhibitory receptors ILT3 and ILT4 on dendritic cells favoring the induction of human CD4+CD25+ Foxp3+ T regulatory cells.

Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45RO+CD25+CD127low regulatory T cells

Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45ro+CD25+CD127(low) regulatory T cells.

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Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45RO+CD25+CD127low regulatory T cells

Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45ro+CD25+CD127(low) regulatory T cells.