Study of Immunomechanisms in HTLV-I-Associated Myelopathy(HAM)

HTLV-I相关性脊髓病（HAM）的免疫机制研究

• 批准号: 63480217
• 负责人: ITOYAMA Yasuto
• 金额: $ 4.03万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480217/
• 关键词: HAM,; HTLV-I,; lymphocyte subsets,; lymphocyte blastoid formation,; NK activity,; CTL activity,; ADCC activity; CTL活性; ADCC活性; HTLV-I; T細胞; グリア障害性; helper inducer T細胞

Purpose :To clarify the pathogenesis of HTLV-I-associated myelopathy (HAM), we studied several immunological abnormalities which were frequently observed in the patients and were thought to be changes characteristic of this disease. In this study, we mainly studied (1) an alteration of subsets of the peripheral blood mononuclear cells (PBMNC), (2) a great increase in spontaneous proliferation of the peripheral blood lymphocytes (PBL), and (3) cellular immune surveillance against increased HTLV-I infected cells in the peripheral circulation of the patients.Results :(1) Subsets of PBMNC ; We found a significant increase in activated T-lymphocytes (CD25+CD3+ cells, CD4+DR+ cells and CD8+DR+ cells) and helper inducer T-lymphocytes (CD4+CD29+ cells) in the peripheral blood of HAM patients. This increase in activated T-lymphocytes and helper T-lymphocytes became more prominant when PBMNC were cultured in a short term. There were decreases in several subsets of NK cells, such as CD16+ cells, … More CD56+ cells and CD16+CD3+ cells.(2) Study of an increased spontaneous PBL proliferation ; We observed a great increase in spontaneous PBL proliferation (SPP) in a short-term culture of PBMNC from HAM patients, without any mitogens or antigens. In the suppression study of the SPP, either the sera from patients or monoclonal antibodies (mAb) to HTLV-I did not suppress the increased SPP. In contrast, mAb to IL-2R (CD25) and cyclosporin A (an inhibitor of IL-2 production) showed strong suppression effects on SPP.(3) Cellular immune surveillance against HTLV-I infected cells ; We observed that HTLV-I proviral DNA was significantly increased in PBMNC from HAM patients compared with those from HTLV-I carriers. To evaluate an ability of the cellular immune surveillance against HTLV-I infected cells, we studied NK activity and CTL and ADCC activities against HTLV-I infected cells. Although CTL activity was significantly higher in HAM patients than in carriers, NK and ADCC activities were significantly decreased in the patients.Conclusions :In the peripheral circulation of HAM patients, HTLV-I infected cells were increased and T-lymphocytes were found in highly activated state. A great increase in SPP is a characteristic change observed in HAM, and the SPP may induce several autoreactive T-cell clones reactive to CNS tissue. Less

目的：为了阐明HTLV-Ⅰ相关性脊髓病（HAM）的发病机制，我们研究了患者中常见的几种免疫学异常，这些异常被认为是这种疾病的特征性变化。本研究主要研究了（1）患者外周血单个核细胞（PBMNC）亚群的变化，（2）患者外周血淋巴细胞（PBL）自发性增殖的显著增加，（3）患者外周循环中HTLV-Ⅰ感染细胞的细胞免疫监视。我们发现HAM患者外周血中活化T淋巴细胞（CD 25 + CD 3+细胞、CD 4 +DR+细胞和CD 8 +DR+细胞）和辅助诱导T淋巴细胞（CD 4 + CD 29+细胞）显著增加。在短期内培养PBMNC时，活化T淋巴细胞和辅助T淋巴细胞的增加变得更加明显。NK细胞的几个亚群，如CD 16+细胞， ...更多信息 CD 56+细胞和CD 16 + CD 3+细胞。(2)PBL自发性增殖增加的研究：我们观察到HAM患者PBMNC在短期培养中的自发性PBL增殖（SPP）显著增加，没有任何促分裂原或抗原。在SPP的抑制研究中，无论是患者血清还是抗HTLV-Ⅰ的单克隆抗体（mAb）都不能抑制SPP的升高。而抗IL-2 R（CD 25）单克隆抗体和IL-2产生抑制剂环孢菌素A（cyclosporin A）对SPP有较强的抑制作用。(3)对HTLV-I感染细胞的细胞免疫监视：我们观察到HTLV-I前病毒DNA显着增加，从HAM患者的PBMNC相比，从HTLV-I携带者。为了评价细胞免疫监视对HTLV-I感染的细胞的能力，我们研究了NK活性和对HTLV-I感染的细胞的CTL和ADCC活性。结论：HAM患者外周血中HTLV-Ⅰ型感染细胞增多，T淋巴细胞处于高度活化状态。SPP的大量增加是在HAM中观察到的特征性变化，并且SPP可以诱导几种对CNS组织反应的自身反应性T细胞克隆。少

项目成果

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Minato, S.：“HTLV-I 相关脊髓病中的活化 T 细胞：自体混合淋巴细胞反应。”Ann.Neurol.26 (1989)。

Itoyama,Y.: "Oncogenic Herpesviruses Recent advances in Japan:Antibody titers to EpsteinーBarr virus in HTLVーI associated myelopathy(HAM)." Hokkaido University Medical Library Series Vol 24, 8 (1988)

Itoyama, Y.：“日本致癌性疱疹病毒的最新进展：HTLV-I 相关脊髓病 (HAM) 中 Epstein-Barr 病毒的抗体滴度。北海道大学医学图书馆系列，第 24 卷，第 8 卷（1988 年）”

Itoyama,Y.: "Neurology and Neurobiology:HTLVーI and the Nervous System:Immunological Aspects of HTLVーIーAssociated Myelopathy(HAM)" Alan R.Liss Inc.New York, 9 (1989)

Itoyama, Y.：“神经学和神经生物学：HTLV-I 和神经系统：HTLV-I 相关脊髓病 (HAM) 的免疫学方面”Alan R.Liss Inc.New York，9 (1989)

Yu, F.: "Natural killer (NK) cells in HTLV-I-associated myelopathy / tropical spastic paraparesis- Decrease in NK subset populations and activity in HTLV-I seropositive individuals-" J. Neuroimmunol.

Yu, F.：“HTLV-I 相关脊髓病/热带痉挛性截瘫中的自然杀伤 (NK) 细胞 - HTLV-I 血清阳性个体中 NK 亚群数量和活性的减少 -”J. Neuroimmunol。

Minato S.: "Expression of HTLV-I antigen in cultured peripheral blood mononuclear cells from patients with HTLV-I associated myelopathy." J.Neurol.Sci.87. 233-244 (1988)

Minato S.：“HTLV-I 相关脊髓病患者培养的外周血单核细胞中 HTLV-I 抗原的表达。”