Expression of T lymphocyte chemoattractants and activation markers in vernal keratoconjunctivitis.
OBJECTIVE
T lymphocytes are present in increased numbers in the conjunctiva of patients with vernal keratoconjunctivitis (VKC) and their activation has a central role in the pathogenesis of the chronic allergic inflammatory reactions seen in VKC. The aims of this study were to examine the expression of three recently described potent T lymphocyte chemoattractants, PARC (pulmonary and activation regulated chemokine), macrophage derived chemokine (MDC), and I-309, the MDC receptor CCR4, and T lymphocyte activation markers, CD25, CD26, CD62L, CD71, and CD30, and to correlate them with the counts of CD3(+) T lymphocytes in the conjunctiva of patients with VKC.


METHODS
Conjunctival biopsy specimens from 11 patients with active VKC, and eight control subjects were studied by immunohistochemical techniques using a panel of monoclonal and polyclonal antibodies directed against PARC, MDC, I-309, CCR4, CD25, CD26, CD62L, CD71, and CD30. The numbers of positively stained cells were counted. The phenotype of inflammatory cells expressing chemokines was examined by double immunohistochemistry.


RESULTS
In the normal conjunctiva, vascular endothelial cells in the upper substantia propria showed weak immunoreactivity for CD26. There was no immunoreactivity for the other antibodies. VKC specimens showed inflammatory cells expressing PARC, MDC, and I-309. The numbers of PARC(+) inflammatory cells were higher than the numbers of MDC(+) and I-309(+) inflammatory cells and the mean values of the three groups differed significantly (17.0 (SD 10.1); 9.5 (9.9), and 4.3 (7.9), respectively, p = 0.0117, ANOVA). The numbers of PARC(+) inflammatory cells had the strongest correlation with the numbers of CD3(+) T lymphocytes. Few CCR4(+) inflammatory cells were observed in only three specimens. Double immunohistochemistry revealed that all inflammatory cells expressing chemokines were CD68(+) monocytes/macrophages. The numbers of CD25(+) T lymphocytes were higher than the numbers of CD26(+), CD62L(+), CD71(+), and CD30(+) T lymphocytes and the mean values of the five groups differed significantly (46.2 (27.9), 30.7 (16.0), 20.1 (8.6), 7.8 (7.7), and 6.5 (4.0), respectively, p <0.001, ANOVA). The numbers of CD25(+) T lymphocytes had the strongest correlation with the numbers of CD3(+) T lymphocytes.


CONCLUSIONS
These results suggest a potential role for PARC, MDC, and I-309 in attracting T lymphocytes into conjunctiva in VKC. T lymphocytes in VKC are activated and express several activation markers which might contribute to the pathogenesis of VKC.
El-Asrar
A M Abu
AM
Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa
Struyf
S
S
Al-Kharashi
S A
SA
Missotten
L
L
Van Damme
J
J
Geboes
K
K
D000293:Adolescent; D000704:Analysis of Variance; D015703:Antigens, CD / Q000276:immunology*; D015415:Biomarkers; D017252:CD3 Complex / Q000276:immunology; D054402:Chemokine CCL1; D054422:Chemokine CCL22; D018925:Chemokines / Q000276:immunology; D019742:Chemokines, CC / Q000276:immunology; D002630:Chemotactic Factors / Q000276:immunology*; D002648:Child; D003228:Conjunctiva / Q000276:immunology; D003233:Conjunctivitis, Allergic / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D015415:Biomarkers; C065971:CCL1 protein, human; C111792:CCL18 protein, human; C515482:CCL22 protein, human; D017252:CD3 Complex; D054402:Chemokine CCL1; D054422:Chemokine CCL22; D018925:Chemokines; D019742:Chemokines, CC; D002630:Chemotactic Factors