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. Conclusion: 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.