RESEARCH ON THE IMMUNOPATHOLOGICAL MECHANISMS OF VOGT-KOYANAGI-HARADA DISEASE

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Vogt-Koyanagi-Harada disease (VKH) is thought to be a systemic disorder affecting various organs containing melanocytes. Melanocyte-specific cytotoxic T lymphocytes (CTL) in VKH have been assumed to be generated and to play an important role in the manifestation of this disease.We established melanoma-specific CTL cell lines from patients with VKH by long term culture of peripheral blood leukocytes with melanoma under IL-2 stimulation. The CTL activity of these cell lines against melanoma was inhibited by the anti-HLA-DR monoclonal antibody, whereas the monoclonal antibody specific for monomorphic determinants of HLA-A,B,and C failed to block lytic activity. Flow cytometric analysis revealed that the surface markers of these cell lines were CD4^+CD8^-HLA_-DR^+CD25^+TCRalphabeta^+TCRgammadelta^-. These cell lines produced extremely high level of IL-6 and Signifioant levels of IL-2 and IFN-gamma.mRNA of IL-2 was detected in the CTLs. Thus, melanoma-specific HLA-DR-restricted T-helper 1 CTLs may play a role in the immunopathogenesis of VKH.We assessed T cell subsets in the peripheral blood and aqueous humor from patients with VKH by using three-color flow cytometry. Although the percentage of CD4^+CD45RA^+ cells within T cells was rare in aqueous humor compared with peripheral blood, the percentage of CD4^+CD29^+ or CD4^+ CD45RO^+ (memory) cells in aqueous humor was much higher than in peripheral blood. Fas antigen, a cell-surface molecule that mediated apoptosis, was expressed preferentially on CD4^+CD45RO^+ cells in aqueous humor. Out results suggest that the accumulation of Fas^+CD4^+CD45RO^+ T lymphocytes in aqueous humor reflects the immunopathological mechanism of VKH.