Plasma macrophage-derived chemokine (CCL22) and its receptor CCR4 on peripheral blood T lymphocytes of asthmatic children

Abstract

Background: The macrophage-derived chemokine (MDC/CCL22) acts on CC chemokine receptor-4 (CCR4) to direct trafficking and recruitment of T helper-2 (TH2) cells into sites of allergic inflammation. It was previously found overexpressed in lesional samples from adult asthmatics. Objective: This study is aimed to investigate the participation of CCR4/MDC axis in the development of TH2-dominated allergen-induced childhood asthma in relation to disease activity, attack severity, and response to therapy, and to outline its value in differentiating atopic asthma from infection-associated airway reactivity. Methods: Proportion of CCR4-expressing peripheral blood T lymphocytes (CCR4+PBTL%) were purified and quantitated by negative selection from peripheral blood mononuclear cells by flow cytometry, and the concentration of MDC in plasma was measured by ELISA in 32 children with atopic asthma (during exacerbation and remission), as well as in 12 children with acute lower respiratory tract infections (ALRTI), and 20 healthy children serving as controls. Results: The mean plasma MDC level (925±471.5 pg/ml) and CCR4+PBTL% (55.3±23.6%) were significantly higher in asthmatic children during acute attacks in comparison to children with ALRTI (109±27.3 pg/ml and 27.6±7.5%) and healthy controls (99.6±25.6 pg/ml and 24.2±4.1%). Both values decreased significantly after subsidence of attacks (502±284.3 pg/ml and 32.5±10.5%) although remained higher than the other 2 groups which were actually comparable in terms of MDC and CCR4%. MDC and CCR4% values were higher among children with acute severe than mild or moderate asthma exacerbations, and in persistent than intermittent cases during stability. Positive correlations could be elicited between both markers during exacerbation or stability, and between the exacerbation level of each and its corresponding value during remission. Corticosteroid-treated patients had the highest expression of both markers when relation to therapy was studied. Conclusion: Our findings reinforce the concept that up regulation of CCR4/MDC axis is implicated in the pathogenesis of pediatric atopic asthma and may represent a useful biomarker of monitoring allergic inflammation and response to therapy. Neutralization and manipulation of CCR4-expressing T cells, as well as MDC antagonism, may represent an adjuvant in the treatment of severe allergic disorders.

Keywords: MDC; CCR4; T-lymphocytes; flowcytometry; asthma; children

Egypt J Pediatr Allergy Immunol 2005; 3(1): 20-31