Expression of chemokine receptors in vernal keratoconjunctivitis

Background/aims-Chemokines are small peptides which are potent activators a nd chemoattractants for leucocyte subpopulations. Their action is mediated by a family of seven transmembrane spanning G-protein coupled receptors. Th e aims of this study were to examine the expression of the chemokine recept ors CCR1, CCR3, CCR5, CXCR3, and CXCR4 in the conjunctiva of patients with vernal keratoconjunctivitis (VKC) and to investigate the phenotype of infla mmatory cells expressing these chemokine receptors. Methods-Conjunctival biopsy specimens from 16 patients with active VKC, and eight control subjects were studied by immunohistochemical techniques usin g 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 i n five of eight specimens. There was no immunoreactivity for CCR1, CCR3, CC R5, and CXCR4. In VKC specimens, membranous immunoreactivity for CXCR3 was noted on inflammatory cells in all specimens. Compared with control specime ns, VKC specimens showed significantly more inflammatory cells expressing C XCR3 (54.3 (SD 34.3) v 3.3 (5.0); p<0.001). Few CCR1(+), CCP3(+), 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 infiltr ating T lymphocytes were reactive for CXCR3. Conclusions-CXCR3 is the predominant chemokine receptor and is expressed ab undantly on T lymphocytes in the conjunctiva of patients with active VKC. T hese 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 suppr ess adverse inflammatory reactions.