Reviews and feature article: Contribution of CCR4 and CCR8 to antigen-specific TH2 cell trafficking in allergic pulmonary inflammation

• Published in: Journal of allergy and clinical immunology 2009-01, Vol.123 (1), p.67-73.e3
• Main Authors: Mikhak, Zamaneh, Fukui, Mieko, Farsidjani, Alireza, Medoff, Benjamin D, Tager, Andrew M, Luster, Andrew D
• Format: Article
• Language: English
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2008.09.049

Background: Interrupting recruitment of allergen-specific TH2 cells to the airway is an attractive potential therapeutic strategy for allergic disease. CC chemokine receptor 4 (CCR4) is preferentially expressed on TH2 cells, and CCR4-expressing cells have been described at sites of allergic inflammation. However, whether selective recruitment of allergen-specific TH2 cells to the airways occurs through CCR4 or other chemokine receptors remains controversial. Objective We investigated the expression of the TH2-associated chemokine receptors (CCR3, CCR4, and CCR8) by primary antigen-specific human airway TH2 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 TH 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 TH2 CCR4+ phenotype. Conclusion We conclude that airway allergen-specific TH2 cells are CCR4+, but in the atopic child CCR4 does not distinguish between recall antigen and allergen specificity.