Chemokine responsiveness of CD4+ CD25+ regulatory and CD4+ CD25- T cells from atopic and nonatopic donors.
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.
Ahern
D
D
Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, UK.
Lloyd
C M
CM
Robinson
D S
DS
D000485:Allergens / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D054398:Receptors, CCR4 / Q000235:genetics / Q000276:immunology*; D054399:Receptors, CCR6 / Q000235:genetics / Q000276:immunology*; D054401:Receptors, CCR8 / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000485:Allergens; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D054398:Receptors, CCR4; D054399:Receptors, CCR6; D054401:Receptors, CCR8