Langerhans' cells in vernal keratoconjunctivitis express the costimulatorymolecule B7-2 (CD86), but not B7-1 (CD80)

Purpose Vernal keratoconjunctivitis (VKC) is associated with T-helper 2 (TH 2)-like cell response and increased immunoglobulin (Ig) E production. Recen t studies have suggested that interactions between costimulatory molecules B7 on antigen-presenting cells and CD28 on T cells are critical for success ful antigen presentation and the development of the TH2 immune response. Th e objective of this study was to examine the expression of costimulatory mo lecules CD28, B7-1 (CD80) and B7-2 (CD86) in conjunctival biopsies from pat ients with active VKC and normal controls. Methods Conjunctival biopsy specimens from 15 subjects with active VKC, and 8 control subjects, were studied by immunohistochemical techniques using a panel of monoclonal and polyclonal antibodies directed against CD28, B7-1 and B7-2 molecules. The phenotype of inflammatory cells expressing costimul atory molecules was examined by sequential double immunohistochemistry. Results In the normal conjunctiva, B7-2 was expressed on a few mononuclear cells in the epithelium and substantia propria in 5 of 8 specimens. There w as no immunoreactivity for CD28 or 137-1. In VKC specimens, few B7-1(+) mon onuclear cells were noted in the substantia propria in 7 of 15 specimens. B 7-2 was expressed on mononuclear cells in the epithelium and substantia pro pria in all specimens. Compared with normal controls, VKC specimens showed significantly more mononuclear cells expressing B7-2 (30.5 +/- 14.1 vs 1.88 +/- 2.5; p < 0.001). In VKC specimens, the numbers of mononuclear cells ex pressing B7-2 were significantly higher than the numbers of mononuclear cel ls expressing B7-1 (30.3 +/- 14.1 vs 2.3 +/- 3.1; p < 0.001). CD28 was expr essed on mononuclear cells in the epithelium and substantia propria in 14 s pecimens. Colocalisation studies revealed that the majority of mononuclear cells expressing B7-2 were CD1a(+) Langerhans' cells, and that the mononucl ear cells expressing CD28 were CD3(+) T lymphocytes. Conclusions B7-2 is more widely and prominently expressed by Langerhans' ce lls compared with B7-1. The interaction of B7-2 with CD28 may mediate the d evelopment of the TH2 immune response in VKC. Thus the manipulation of this pathway could be an important target for the development of future therapi es in VKC.