1995 Fiscal Year Final Research Report Summary
RESEARCH ON THE IMMUNOPATHOLOGICAL MECHANISMS OF VOGT-KOYANAGI-HARADA DISEASE
| Project/Area Number |
06671757
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Ophthalmology
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
NOROSE Kazumi SHINSHU UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF OPHTHALMOLOGY ASSISTANT PROFESSOR, 医学部・眼科, 助教授 (30156244)
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| Co-Investigator(Kenkyū-buntansha) |
YANO Akihiko NAGASAKI UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICALZOOLOGY PROFESSOR, 医学部・医動物学, 教授 (20135122)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Vogt-koyanagi-harada disease / Aqueous humor / Flowcytimetry / Uveitis / Activatedt cells / Fas / Apoptosis / Memory T cells |
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| Research Abstract |
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.
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