T Cell & HLA-DR Antigen In The Pathogenesis Of Proliferative Vitreoretinopathy

T cell & HLA-DR antigen in the pathogenesis of Proliferative VitreoretinopathyM.S. Candidate: Wenji Zhang Director: Yannian HuiDepartment of Ophthalmology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, P.R. ChinaAim: Proliferative vitreoretinopathy (PVR) is an excessive wound healing response that involved many kinds of inflammatory cytokines, and migration and proliferation of cells. Macrophages have been proved to play an important roll in the development of PVR, but there are evidences that other types of white blood cells are indispensable in the pathogenesis of PVR. This experiment aims: (1) to characterize the infiltrating inflammatory cells in proliferative membranes surgically removed from the eyes of PVR; (2) to investigate the ability of retinal pigment epithelial (RPE) cells to express human leukocyte antigen (HLA)-DR antigens under the induction of Interferon-gamma (IFN- γ)?Methods: (1) Specimens were obtained during vitreoretinal surgery, including fluid collections of PVR grade B, and epiretinal membranes from PVR grade C or D, Immunohistochemical detection was performed to examine the presence CD3, CD4, or CD8 markers and HLA-DR antigen positive cells in these specimens; (2) Human RPE cells were cultured in the presence of interferon-gamma (IFN-γ)(10,50,100,500,1000U/ml) and then stained immunohistochemically for HLA-DR antigen. HLA-DR antigen expression levels are examined by the percentage of positive-stained RPE cells. Results: (1) CD3 positive cells were found in 6 of 7 specimens of PVR B grade, andCD4 positive cells were present in 2 of the 6 CDS positive specimens. CDS markers expression was negative in all specimens. MHC class II antigen HLA-DR were positive in 2 specimens. In 14 PVR C/D membranes, lymphocytes expressing CDS markers were observed in all, whilst T lymphocytes expressing CD4 and CDS markers were found in 10 and 5 of 14 membranes, respectively. Positive staining for HLA-DR was found in 9 of 14 membranes. (2) HRPE cells cultured with a single dose of 50-1000 U/ml IFN- Y for up to 6 days express HLA-DR molecule in a dose dependent manner. After removal of IFN- Y stimulus, HLA-DR antigen expression persisted for at least 8 days.Conclusion: (1) The present findings indicate that T lymphocytes are present in PVR proliferative membranes and may be activated. (2) IFN- Y induce MHC class II molecules (HLA-DR) expression on human RPE cells in a dose dependent manner. This indicates that RPE cells inducted to express HLA-DR may act as local antigen presenting cells (APC) to incite T cell mediated immunity in the development of PVR.