T lymphocytes expressing CCR3 are increased in allergic rhinitis compared with non-allergic controls and following allergen immunotherapy.
BACKGROUND
In T cell-associated allergic inflammation, homing of T-helper 2 (Th2) effector cells to mucosal sites may be influenced by chemokine receptor expression. Previous studies have identified CCR3 and CCR4 as putative markers of Th2 cells and CCR5 and CXCR3 as markers of Th1 cells. The aim of this study was to assess differential chemokine receptor expression from symptomatic atopic grass pollen-sensitive subjects, compared with patients on high-dose allergen injection immunotherapy (IT) and healthy controls.


METHODS
We examined chemokine receptor expression (CCR1-7 and CXCR1-4) by flow cytometry of peripheral blood CD4+ and CD8+ T cells. We also depleted peripheral blood mononuclear cell (PBMC) populations of CCR3+ CD4+ cells by magnetic bead separation and cells were stimulated with grass pollen allergen for 6 days. Cytokine production was measured by enzyme-linked immunosorbent assay.


RESULTS
On freshly isolated PBMC, atopic individuals exhibited increased numbers of CCR3+ CD4+ cells compared with normal controls (P < 0.01). CCR3 expression in IT patients was reduced compared with matched atopic rhinitic controls (P < 0.05) and comparable with that observed in normal subjects. Depletion of CCR3+ CD4+ cells from allergen-stimulated PBMC cultures resulted in decreased interleukin (IL)-5 production compared with whole CD4+ populations (P < 0.05). Freshly isolated CCR3+ CD4+ cells have significantly higher intracellular IL-4 and lower IFN-gamma levels than CCR3- CD4+ cells. CD4+ T cells cultured from both peripheral cells and nasal biopsies demonstrated increased expression of CCR3 in the presence of IL-4 (P < 0.05).


CONCLUSIONS
CCR3+ CD4+ T cells are increased in allergic rhinitis, are reduced by allergen IT, have a Th2 phenotype and contribute to allergen-specific responses. Strategies against CCR3+ T cells may be effective in human allergic diseases.
Francis
J N
JN
Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
Lloyd
C M
CM
Sabroe
I
I
Durham
S R
SR
Till
S J
SJ
D000328:Adult; D002452:Cell Count; D002478:Cells, Cultured; D003888:Desensitization, Immunologic; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D006109:Poaceae / Q000276:immunology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology* / Q000378:metabolism*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism
C515350:CCR3 protein, human; D015848:Interleukin-5; D054397:Receptors, CCR3; D019707:Receptors, Chemokine