| Project/Area Number |
14370209
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kyushu University |
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Principal Investigator |
KIRA Jun-ichi Kyushu University, Department of Neurology, Prof., 大学院・医学研究院, 教授 (40183305)
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| Co-Investigator(Kenkyū-buntansha) |
OCHI Hirofumi Kyushu University, Department of Neurology, Assistant Prof., 大学病院, 講師 (20325442)
NISHIMURA Yasuharu Kumamoto University, Division of Immunogenetics, Prof., 大学院・医学研究院, 教授 (10156119)
MURAI Hiroyuki Kyushu University, Department of Neurology, Clinical Instructor, 大学病院, 助手 (80325464)
OSOEGAWA Manabu Kyushu University, Department of Neurology, Clinical Instructor, 大学病院, 助手
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2003: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2002: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | multiple sclerosis / opticospinal / hsp105 / HLA class II / transgenic mouse / SEREX / HSP105 |
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| Research Abstract |
1.Identification of a novel autoantigen hsp105 in patients, with multiple sclerosis
To discover novel autoantigens in Japanese patients with multiple sclerosis(MS), we immunoscreened spinal cord-derived cDNA library with sera from 8 MS patients(5-10×10^5 clones screened in each patient). One of five positive clones was heat shock protein 105(hsp105), which is expressed most abundantly in the brain. We then examined immune responses to hsp105 in MS patients and found that (1)the frequency of anti-hsp105 IgG antibody increased in MS patients than in controls, (2)hsp105 expression was enhanced in the MS lesions and EAE, (3)significant proliferation of CD4^+CD45RO^+T cell to hsp105 was noted only in MS patients, (4)in the ELISPOT assay, IL-10 response to hsp105 was significantly higher than IL-4 and IFN-gamma responses to hsp105 in both MS patients and healthy controls, however the IL-10 response was significantly lower as compared with controls. These findings suggest the immune response to hsp105 in human and that the response is attenuated in MS patients. Furthermore, we studied immunogenicity of hsp105 in mice and found that (5)immunization with either human or autologous mouse hsp105 did not induce EAE, (6)mice vaccinated with pHSP105showed marked exacerbation of EAE. In future, we are going to analyze the mechanism of exacerbation of EAE by pHSP105.
2.Animal model of opticospinal form of multiple sclerosis
In Japan, susceptibility to OS-MS is associated with the HLA-DPB1*0501 allele. HLA-DP5(DPA1*02022/DPB1*0501) transgenic mice were generated by co-injection of the HLA-DPA1*02022/pDOI-6 fragment and HLA-DPB1*0501/pDOI-6 fragment into fertilized mouse eggs(C57BL/6). The resulting mice were tested for integration of the transgene by PCR analysis of tail DNA. Now, transgenic lines derived from three independent founders are tested for expression of HLA-DPA1*02022 RNA and HLA-DPB1*0501 RNA in thymus and spleen.
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