GAMMA-INTERFERON INDUCES DIFFERENTIAL EXPRESSION OF HLA-DR, HLA-DP AND HLA-DQ IN HUMAN CILIARY EPITHELIAL-CELLS

The antigen-specific activation of T-helper lymphocytes is dependent on the presentation of antigen in context with the gene products of the major histocompatibility complex class II (MHC II). Aberrant expression of MHC II on the ciliary epithelium has been observed in uveitic eyes which may enable these cells to specifically interact with lymphocytes and may play a role in ocular autoimmunity. Human MHC II consists of three subclasses termed HLA-DR, -DP and -DQ, which seem to be differentially regulated and may have different functions. The present study was initiated to investigate the dynamics of the differential MHC II expression on cultured human non-pigmented ciliary epithelial cells (NPE cells) in response to gamma-interferon (gamma-IFN) by means of immunohistochemistry. NPE cells grown in control tissue-culture medium did not express MHC class II. HLA-DR and -DP could be induced by incubation with 100 u/ml gamma-IFN for 3 days. HLA-DQ was expressed only weakly and at higher doses of gamma-IFN (greater-than-or-equal-to 500 u/ml) and longer incubation periods (greater-than-or-equal-to 5 days). After removal of the gamma-IFN stimulus, all three MHC II subclasses persisted for several days. The differential expression of HLA-DR and -DP as compared with HLA-DQ in response to gamma-IFN in the ciliary epithelium is similar to observations in other non-lymphoid ocular cells but appears to be different from the regulation of MHC II expression on lymphoid cells. Since HLA-DR and -DP seem to be linked mainly to immune-response genes, whereas a linkage to immune suppressor genes has been described for HLA-DQ, the MHC II expression on bone marrow-derived cells and non-lympoid ocular cells may serve different functions.