Adenoid-derived TH2 cells reactive to allergen and recall antigen express CC chemokine receptor 4.
BACKGROUND
Interrupting recruitment of allergen-specific T(H)2 cells to the airway is an attractive potential therapeutic strategy for allergic disease. CC chemokine receptor 4 (CCR4) is preferentially expressed on T(H)2 cells, and CCR4-expressing cells have been described at sites of allergic inflammation. However, whether selective recruitment of allergen-specific T(H)2 cells to the airways occurs through CCR4 or other chemokine receptors remains controversial.


OBJECTIVE
We investigated the expression of the T(H)2-associated chemokine receptors (CCR3, CCR4, and CCR8) by primary antigen-specific human airway T(H)2 cells.


METHODS
Children undergoing elective adenoidectomy were recruited, and their atopic status was determined. Adenoid cells were cultured with allergen or recall antigen. Flow cytometric analyses permitted identification of T(H) cells proliferating in response to antigen and characterization of chemokine receptor and cytokine expression.


RESULTS
An increased proportion of airway CD4(+) T cells proliferated to allergen in atopic children (n = 6, of which 4 were given diagnoses of asthma or rhinitis) compared with nonatopic children (P =.0004). These cells were 44.7% (32.6% to 50.0%) IL-4(+) and only 2.5% (0.6% to 3.3%) IFN-(gamma) and showed a greater than 5-fold upregulation of CCR4 expression to 54.0% (40.7% to 67.8%) after culture, whereas CCR3 was expressed on 9.7% (7.4% to 18.9%) of allergen-reactive cells and CCR8 on less than 1%. Interestingly, increased expansion of recall antigen-specific cells was also seen in atopic children, and these cells were also predominantly of a T(H)2 CCR4(+) phenotype.


CONCLUSIONS
We conclude that airway allergen-specific T(H)2 cells are CCR4(+), but in the atopic child CCR4 does not distinguish between recall antigen and allergen specificity.
Banwell
Miles E
ME
Leukocyte Biology Biomedical Sciences Division, Faculty of Medicine, Imperial College, London, United Kingdom.
Robinson
Douglas S
DS
Lloyd
Clare M
CM
D000234:Adenoids / Q000166:cytology / Q000276:immunology*; D000485:Allergens / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003546:Cysteine Endopeptidases; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D031784:Phleum / Q000276:immunology; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D000941:Antigens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C515354:CCR4 protein, human; D017252:CD3 Complex; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1