Expression of chemokine receptors in vernal keratoconjunctivitis

Abstract

Background/aims: Chemokines are small peptides which are potent activators and chemoattractants for leucocyte subpopulations. Their action is mediated by a family of seven transmembrane spanning G-protein coupled receptors. The aims of this study were to examine the expression of the chemokine receptors CCR1, CCR3, CCR5, CXCR3, and CXCR4 in the conjunctiva of patients with vernal keratoconjunctivitis (VKC) and to investigate the phenotype of inflammatory cells expressing these chemokine receptors.

Methods: Conjunctival biopsy specimens from 16 patients with active VKC, and eight control subjects were studied by immunohistochemical techniques using a panel of monoclonal antibodies directed against human CCR1, CCR3, CCR5, CXCR3, and CXCR4. The phenotype of inflammatory cells expressing chemokine receptors was examined by double immunohistochemistry.

Results: In the normal conjunctiva, few inflammatory cells expressed CXCR3 in five of eight specimens. There was no immunoreactivity for CCR1, CCR3, CCR5, and CXCR4. In VKC specimens, membranous immunoreactivity for CXCR3 was noted on inflammatory cells in all specimens. Compared with control specimens, VKC specimens showed significantly more inflammatory cells expressing CXCR3 (54.3 (SD 34.3) v 3.3 (5.0); p<0.001). Few CCR1+, CCR3+, CCR5+, and CXCR4+ inflammatory cells were observed in only three of 16 specimens. Double immunohistochemistry revealed that all CXCR3 positive inflammatory cells were CD3 positive T lymphocytes and that 61.7% (3.7%) of the infiltrating T lymphocytes were reactive for CXCR3.

Conclusions: CXCR3 is the predominant chemokine receptor and is expressed abundantly on T lymphocytes in the conjunctiva of patients with active VKC. These data suggest a potential role for CXCR3 receptors in the regulation of lymphocyte recruitment within conjunctiva of VKC patients. New therapeutic strategies that block CXCR3 may inhibit T lymphocyte recruitment and suppress adverse inflammatory reactions.

Figure 1

Vernal keratoconjunctivitis. Immunohistochemical staining for CXCR3. Low power (A) (×500) and high power (B) (×1200) views showing membranous immunoreactivity on mononuclear cells (arrows), as well as in the intercellular spaces (arrowheads).

Figure 2

Vernal keratoconjunctivitis. Double immunohistochemistry for CXCR3 (red), and CD3 (blue). Low power (×500) and high power (×1200) (inset) views showing CXCR3 positive cells coexpressing CD3 marker (arrows).