CCR4 and CCR5 expression in conjunctival specimens as differential markers of TH1/TH2 in ocular surface disorders

Background: Accurate inflammatory mechanisms in chronic ocular surface diseases (OSDs) cannot routinely be assessed. New techniques for investigating ocular surface inflammatory pathways are of major importance. Objective: To investigate the expressions of CCR4 and CCR5, known to be related to the T(H)2 and T(H)1 systems, respectively, and HLA-DR in conjunctival impression cytology specimens from patients with chronic OSDs. Methods: In this case-controlled study, impression cytology specimens were taken in a series of patients with vernal keratoconjunctivitis (n = 21), giant papillary conjunctivitis (n = 6), or keratoconjunctivitis sicca (KCS; n = 17), or receiving topical antiglaucoma treatments (n = 31), and from 20 normal subjects. Conjunctival cells were incubated with mAbs to CCR4, CCR5, CD45, and HLA-DR to quantify conjunctival inflammation in a masked manner using flow cytometry. Results: HLA-DR was higher in the glaucoma and KCS groups than in allergic and normal eyes. CCR4 was overexpressed in allergy and glaucoma, whereas CCR5 was higher in the KCS and glaucomatous groups. CD45 was expressed by only few cells in all groups, with almost no significant differences. CCR4 expression was negatively correlated with CCR5 and HLA-DR, whereas CCR5 was positively correlated with HLA-DR. Conclusion: This study confirms the overexpression of chemokine receptors by the conjunctival epithelium in OSDs. CCR4 and CCR5 expression may vary according to the immune pathway involved. Accurate mechanisms in ocular surface inflammatory reactions-that is, those related to the T(H)1 or T(H)2 systems-could be differentiated by CCR4/CCR5 profiles. Our results also suggest that long-term use of topical treatments may stimulate both systems.