Project/Area Number |
07670283
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Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
寄生虫学(含医用動物学)
|
Research Institution | Chiba University (1996) Nagasaki University (1995) |
Principal Investigator |
YANO Akihiko Chiba Univ.Sch.Med., Dept of Parasitology, Professor, 医学部, 教授 (20135122)
|
Co-Investigator(Kenkyū-buntansha) |
AOSAI Fumie Nagasaki Univ.Sch.Med., Dept of Med.Zoology, Lecturer, 医学部, 講師 (80150316)
由井 克之 長崎大学, 医学部, 講師 (90274638)
野呂瀬 一美 信州大学, 医学部, 助教授 (30156244)
|
Project Period (FY) |
1995 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
Keywords | Toxoplasmic retinochoroiditis / CD4^+CTL / Toxoplasma gondii / Melanoma / gamma-IFN / Uveitis / SAG1 gene / Quantitative competitive PCR / γ-IFN / IL-6 |
Research Abstract |
The most severe clinical symptoms of congenital toxoplasmosis are retinochoroiditis, encephalomyelitis and hydrocephalus, skin rush, together with hepatosplenomegaly and lymphadenopathy. Some of these organs and tissues contain melanocytes. Vogt-Koyanagi-Harada disease ahs believed as an autoimmune disease in which melanocytes are target cells of autoimmune responses in the patients. To examine the possibility of the mechanisms operative in toxoplasmic retinochoroiditis and Vogt-Koyanagi-Harada disese, we analyzed the cytotoxic responses of PBL of toxoplasmosis patients which were induced by Toxoplasma gindii (T.gondii) -infected melanoma cells and of PBL of Vogt-Koyanagi-Harada disease induced by melanoma cells. T.gondii-infected human melanoma cell-specific CD4+CTL were induced from the PBL of patients with toxoplasmosis by stimulation with T.gondii-infected melanoma cells. Similarly, melanoma-specific CD4+CTL cells were induced from PBL of Vogt-Koyanagi-Harada disease by the stimulation HLA-DR matched melanoma cells. These CD4+CTL cells produced a large amount of IFN-gamma and IL-6 in response to the stimulation by T.gondii-infected melanoma cells in toxoplasmosis patients or melanoma cells in Vogt-Koyanagi-Harada disease. HLA-DR expression of T.gondii-infected melanoma cells was upregulated by both IFN-gamma and IL-6, but antigen presentation of T.gondii-infected melanoma cells to T.gondii-infected cell-specific CD4+CTL was upregulated by only IFN-gamma but not by IL-6. Thus, human melanocytes infected by T.gondii may play an important role in immunopathogenic as in toxoplasmic chorioretinitis through the production of these lymphokines. Similarly, melanocytes may be immunopathogenic in Vogt-Koyanagi-Harada diseas.
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