CCR 4 and CCR 5 expression in conjunctival specimens as differential markers of T(H)1/ T(H)2 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 CCR 4 and CCR 5, 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 CCR 4, CCR 5, 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. CCR 4 was overexpressed in allergy and glaucoma, whereas CCR 5 was higher in the KCS and glaucomatous groups. CD45 was expressed by only few cells in all groups, with almost no significant differences. CCR 4 expression was negatively correlated with CCR 5 and HLA-DR, whereas CCR 5 was positively correlated with HLA-DR.


CONCLUSIONS
This study confirms the overexpression of chemokine receptors by the conjunctival epithelium in OSDs. CCR 4 and CCR 5 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 CCR 4/CCR 5 profiles. Our results also suggest that long-term use of topical treatments may stimulate both systems.
Baudouin
Christophe
C
Department of Ophthalmology, Quinze-Vingts National Ophthalmology Hospital and Ambroise Paré Hospital, APHP, Paris-Ouest School of Medicine, University of Versailles, Paris, France. baudouin@quinze-vingts.fr
Liang
Hong
H
Bremond-Gignac
Dominique
D
Hamard
Pascale
P
Hreiche
Raymond
R
Creuzot-Garcher
Catherine
C
Warnet
Jean-Michel
JM
Brignole-Baudouin
Françoise
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D003229:Conjunctival Diseases / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008875:Middle Aged; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D015415:Biomarkers; C515354:CCR4 protein, human; D006684:HLA-DR Antigens; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens