[Ocular infiltrating CD 4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens].
Vogt-Koyanagi-Harada (VKH) disease is a systemic disorder affecting systemic melanocytes including those in the eyes, meninges, ears, skin, and hair. Although the pathogenic mechanisms of the disease are still controversial, there is clinical and experimental evidence that the disease is an autoimmune disease involving melanocytes. In this study, we investigated whether patients with VKH disease have immune responses specific to melanocyte antigens, and whether T lymphocytes of these patients cross-react with peptides of melanocytes and with exogenous antigens. Cells infiltrating the eyes in HLA-DR 4+ patients with VKH contained a population of CD 4+ T lymphocytes that recognized tyrosinase and gp 100 peptides and produced cytokines in response to these two peptides. The CD 8+ T cells recognized the MART-1 melanocyte peptide, but not the CD 4+ T cells. When a search was made for molecular mimicry between melanocyte antigens and exogenous antigens by database screening, cytomegalovirus envelope glycoprotein H (CMV-egH) had high amino acid homology with the tyrosinase peptide. Some of the T cells taken from VKH patients recognized melanocyte peptides including the tyrosinase peptide as well as the CMV-egH290-302 peptide, which had a high amino acid homology to the tyrosinase peptide. CMV peptide-specific T cells showed significant proliferation in response not only to CMV-egH290-302, but also to tyrosinase450-462. The seroprevalence of CMV was significantly higher in VKH patients. In addition, all tested samples of VKH patients were negative for CMV-DNA. These results indicate that CMV infection may stimulate the production of T cells that crossreact with tyrosinase by molecular mimicry. These events may be responsible for the onset of VKH disease.
Sugita
Sunao
S
Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. sunaoph@tmd.ac.jp
D000951:Antigens, Neoplasm / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D058965:MART-1 Antigen; D008544:Melanocytes / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology*; D014607:Uveomeningoencephalitic Syndrome / Q000276:immunology*
D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins