| Project/Area Number |
10670570
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | TOHOKU UNIVERSITY |
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Principal Investigator |
FUJIHARA Kazuo Tohoku University Hospital, Lecturer, 医学部・附属病院, 講師 (70280873)
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| Co-Investigator(Kenkyū-buntansha) |
ONODERA Hiroshi Tohoku University School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20214207)
ITOYAMA Yasuto Tohoku University School of Medicine, Professor, 大学院・医学系研究科, 教授 (30136428)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | HTLV-I / HAM / ADCC / K cell / NK-T cell / immunesurveillance / retrovirus / myelopathy |
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| Research Abstract |
Antibody-dependent cell-mediated cytotoxicity (ADCC) is impaired in HTLV-I associated myelopathy (HAM). This defect in immune surveillance may allow the increased replication of human T-lymphotropic virus type I (HTLV-I) in HAM. Thus, we studied factors influencing the impaired anti-HTLV-I ADCC in HAM. (1) Peripheral blood mononuclear cells (PBMC) in HAM and controls were pre-incubated with cytokines such as interleukin-2, interferon-alpha, and interferon-gamma, and then were used in ADCC assay. The ADCC activities were augmented in all the control subject, but they were further impaired in more than half of the patients with HAM. (2) Protein G-treated sera of HAM did not show any anti-HTLV-I ADCC activity, indicating that the ADCC antibodies were of lgG class. (3) Inhibition of HTLV-I tax expression by anti-sense methodology did not alter the anti-HTLV-I ADCC activity. (4) CD3+CD16+cell subset showed 1/3〜1/4 of the total ADCC effector activity. We previously reported a decrease in CD56+cell subset, an NK-T cell marker, in HAM. We studied anti-HTLV-I immunesurveillance by NK-T cells in HAM. (5) PBMC of the patients with HAM treated with anti-CD16 antibody completely abolished the anti-HTLV-I ADCC activity. In contrast, anti-CD56 and CD57 antibodies did not show such inhibition. (6) NK-T cells did not show any significant cytotoxicity against HTLV-I infected cells. (7) HTLV-I genome was not detected in NK-T cells. The impaired ADCC effector activity may attributable to the immunomodulating effects of some humoral factors, such as the cytokines in the present study. A vigorous search for identifying factors to augment the ADCC effector activity is needed to develop a therapeutically effective immunesurveillance against human retroviruses.
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