Chemokine responsiveness of CD4+ CD25+ regulatory and CD4+ CD25- T cells from atopic and nonatopic donors. 2009

D Ahern, and C M Lloyd, and D S Robinson
Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, UK.

BACKGROUND Allergic inflammation is associated with Th2-type T cells, which can be suppressed by CD4+ CD25+ regulatory T cells (Tregs). Both express chemokine receptors (CCR) 4 and CCR8, but the dynamics of expression and effect of atopic status are unknown. OBJECTIVE To examine the expression of chemokine receptors by CD4+ CD25+ and CD4+ CD25- T cells from atopic and nonatopic donors, and document response to allergen stimulation in vitro. METHODS Chemokine receptor expression was examined by flow cytometry and quantitative PCR of CD4+ CD25hi and CD4+ CD25- T cells from atopics and nonatopics. Responsiveness to chemokines was by actin polymerization. Dynamics of chemokine receptor expression in 6-day allergen-stimulated cultures was analysed by carboxyfluoroscein succinimidyl ester labelling. RESULTS CD4+ CD25hi Tregs preferentially expressed CCR3, CCR4, CCR5, CCR6 and CCR8. CD4+ CD25hi Tregs responded to the chemokine ligands for CCR4, CCR6 and CCR8 (CCL17, 22, 20 and 1 respectively), with no differences between atopic and nonatopic donors. Over 6-day allergen stimulation, CD4+ CD25+ T-cells downregulated CCR4 and upregulated CCR7, in contrast to CD4+ CD25- effector cells, which downregulated CCR7 and upregulated CCR4. CONCLUSIONS CCR4, CCR6 and CCR8 have potential roles in localization of both CD4+ CD25+ regulatory and CD4+ CD25- effector T cells to sites of allergic inflammation. Upregulation of CCR7 and downregulation of CCR4 upon allergen stimulation of Tregs may allow their recirculation from sites of inflammation, in contrast to retention of effector T cells.

UI MeSH Term Description Entries
D006969 Hypersensitivity, Immediate Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigen-antibody reaction and causes smooth muscle contraction and increased vascular permeability. Atopic Hypersensitivity,Hypersensitivity, Atopic,Hypersensitivity, Type I,IgE-Mediated Hypersensitivity,Type I Hypersensitivity,Atopic Hypersensitivities,Hypersensitivities, Atopic,Hypersensitivities, IgE-Mediated,Hypersensitivities, Immediate,Hypersensitivities, Type I,Hypersensitivity, IgE-Mediated,IgE Mediated Hypersensitivity,IgE-Mediated Hypersensitivities,Immediate Hypersensitivities,Immediate Hypersensitivity,Type I Hypersensitivities
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000485 Allergens Antigen-type substances that produce immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE). Allergen
D015704 CD4 Antigens 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. They are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. T4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120. Antigens, CD4,CD4 Molecule,CD4 Receptor,CD4 Receptors,Receptors, CD4,T4 Antigens, T-Cell,CD4 Antigen,Receptors, Surface CD4,Surface CD4 Receptor,Antigen, CD4,Antigens, T-Cell T4,CD4 Receptor, Surface,CD4 Receptors, Surface,Receptor, CD4,Surface CD4 Receptors,T-Cell T4 Antigens,T4 Antigens, T Cell
D050378 T-Lymphocytes, Regulatory CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells. Regulatory T Cell,Regulatory T-Cell,Regulatory T-Lymphocyte,Regulatory T-Lymphocytes,Suppressor T-Lymphocytes, Naturally-Occurring,T-Cells, Regulatory,Th3 Cells,Tr1 Cell,Treg Cell,Regulatory T-Cells,Suppressor T-Cells, Naturally-Occurring,Tr1 Cells,Treg Cells,Cell, Regulatory T,Cell, Th3,Cell, Tr1,Cell, Treg,Cells, Regulatory T,Cells, Th3,Cells, Tr1,Cells, Treg,Naturally-Occurring Suppressor T-Cell,Naturally-Occurring Suppressor T-Cells,Naturally-Occurring Suppressor T-Lymphocyte,Naturally-Occurring Suppressor T-Lymphocytes,Regulatory T Cells,Regulatory T Lymphocyte,Regulatory T Lymphocytes,Suppressor T Cells, Naturally Occurring,Suppressor T Lymphocytes, Naturally Occurring,Suppressor T-Cell, Naturally-Occurring,Suppressor T-Lymphocyte, Naturally-Occurring,T Cell, Regulatory,T Cells, Regulatory,T Lymphocytes, Regulatory,T-Cell, Naturally-Occurring Suppressor,T-Cells, Naturally-Occurring Suppressor,T-Lymphocyte, Regulatory,Th3 Cell
D053645 Interleukin-2 Receptor alpha Subunit A low affinity interleukin-2 receptor subunit that combines with the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN to form a high affinity receptor for INTERLEUKIN-2. Antigens, CD25,CD25 Antigens,Interleukin-2 Receptors alpha,Tac P55 Peptide,CD25 Antigen,IL-2Ralpha,Interleukin-2 Receptor alpha,Interleukin-2 Receptor alpha Chain,Interleukin-2Ralpha,alpha-subunit, Receptor, Interleukin-2,Antigen, CD25,IL 2Ralpha,Interleukin 2 Receptor alpha,Interleukin 2 Receptor alpha Chain,Interleukin 2 Receptor alpha Subunit,Interleukin 2 Receptors alpha,Interleukin 2Ralpha,Receptor alpha, Interleukin-2,Receptors alpha, Interleukin-2
D054398 Receptors, CCR4 CCR receptors with specificity for CHEMOKINE CCL17 and CHEMOKINE CCL22. They are expressed at high levels in T-LYMPHOCYTES; MAST CELLS; DENDRITIC CELLS; and NK CELLS. Antigens, CD194,CC Chemokine Receptor 4,CCR4 Receptors,CD194 Antigens,CC Chemokine Receptors 4,CCR4 Receptor,CD194 Antigen,Antigen, CD194,Receptor, CCR4

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