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(Investigative Ophthalmology and Visual Science. 2006;47:2547-2554.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-1547
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Ocular Infiltrating CD4+ T Cells from Patients with Vogt-Koyanagi-Harada Disease Recognize Human Melanocyte Antigens

Sunao Sugita,1 Hiroshi Takase,1 Chikako Taguchi,2 Yasuhisa Imai,1 Koju Kamoi,1 Tatsushi Kawaguchi,1 Yoshiharu Sugamoto,1 Yuri Futagami,1 Kyogo Itoh,3 and Manabu Mochizuki1

1From the Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan; the 2Departments of Ophthalmology and 3Immunology, Kurume University School of Medicine, Fukuoka, Japan.

PURPOSE. To determine whether patients with Vogt-Koyanagi-Harada (VKH) disease have immune responses specific to the melanocyte antigens tyrosinase and gp100.

METHODS. T-cell clones (TCCs) were established from cells infiltrating the aqueous humor and from peripheral blood mononuclear cells (PBMCs) of patients with VKH. The target cells were LDR4-transfected cells (HLA-DRB1*0405). The TCCs were cocultured with LDR4 in the presence of tyrosinase (tyrosinase450-462: SYLQDSDPDSFQD), gp100 (gp10044-59: WNRQLYPEWTEAQRLD), or a control peptide. The immune response was evaluated by cytokine production. The responding melanocyte peptide-specific VKH-TCCs were characterized by an immunofluorescence method with flow cytometry. A search was made for molecular mimicry among tyrosinase450-462, gp10044-59, and exogenous antigens, such as viruses, by database screening.

RESULTS. Cells infiltrating the eye and PBMCs in HLA-DR4+ (HLA-DRB1*0405, 0410) patients with VKH contained a population of CD4+ T lymphocytes that recognized tyrosinase and gp100 peptides and produced RANTES and IFN-{gamma} in response to the two peptides. The T cells were active memory Th1-type lymphocytes, and they recognized the tyrosinase peptide and produced IFN-{gamma} in response to HLA-DRB1*0405+ melanoma cells. Cytomegalovirus envelope glycoprotein H (CMV-egH290-302) had high amino acid homology with the tyrosinase peptide. In addition, some of the VKH-TCCs recognized CMV-egH290-302 peptide, as well as the tyrosinase peptides.

CONCLUSIONS. In VKH there are tyrosinase and gp100 peptide-specific T cells that can mediate an inflammatory response. Such melanocyte antigen-specific T cells could be associated with the cause and pathology of VKH disease.




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