The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics

In vitro polarized human Th2 cells preferentially express the chemokine rec eptors CCR3, CCR4, and CCR8 and migrate to their ligands: eotaxin, monocyte -derived chemokine (MDC), thymus- and activation-regulated chemokine (TARC) , and I-309. We have studied the expression of chemokines and chemokine rec eptors in the airway mucosa of atopic asthmatics. Immunofluorescent analysi s of endobronchial biopsies from six asthmatics, taken 24 hours after aller gen challenge, demonstrates that virtually all T cells express IL-4 and CCR 4. CCR8 is coexpressed with CCR4 on 28% of the T cells, while CCR3 is expre ssed on eosinophils but not on T cells. Expression of the CCR4-specific lig ands MDC and TARC is strongly upregulated on airway epithelial cells upon a llergen challenge, suggest ing an involvement of this receptor/ligand axis in the regulation of lymphocyte recruitment into the asthmatic bronchi. In contrast to asthma, T cells infiltrating the airways of patients with chron ic obstructive pulmonary disease and pulmonary sarcoidosis produce IFN-gamm a and express high levels of CXCRS3, while lacking CCR4 and CCR8 expression . These data support the role of CCR4, of its ligands MDC and TARC, and of CCR8 in the pathogenesis of allergen-induced late asthmatic responses and s uggest that these molecules could be considered as targets for therapeutic intervention.