The Pathomechanisms of The Impaired Anti-HTLV-I Immunesurveillance by ADCC in HAM

HAM中ADCC抗HTLV-I免疫监视受损的发病机制

基本信息

批准号：
10670570
负责人：
FUJIHARA Kazuo
金额：
$ 1.02万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670570/
关键词：
HTLV-I HAM ADCC K cell NK-T cell immunesurveillance retrovirus myelopathy

项目摘要

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.

HTLV-I 相关性脊髓病 (HAM) 中的抗体依赖性细胞介导的细胞毒性 (ADCC) 受损，这种免疫监视缺陷可能导致 HAM 中人类 T 淋巴细胞病毒 (HTLV-I) 的复制增加。我们研究了影响 HAM 中抗 HTLV-I ADCC 受损的因素 (1) 将 HAM 和对照中的外周血单核细胞 (PBMC) 与细胞因子一起预孵育。白细胞介素-2、干扰素-α 和干扰素-γ，然后用于 ADCC 测定，所有对照受试者的 ADCC 活性均增强，但超过一半的 HAM 患者的 ADCC 活性进一步受损 (2)。蛋白G处理的HAM血清没有显示任何抗HTLV-I ADCC活性，表明ADCC抗体属于IgG类(3)反义对HTLV-Itax表达的抑制。 (4) CD3+CD16+细胞亚群显示出总ADCC效应活性的1/3〜1/4，我们之前报道了CD56+细胞亚群（NK）的减少。 -T 细胞标记，在 HAM 中，我们研究了 HAM 中 NK-T 细胞的抗 HTLV-I 免疫监视作用。 (5) 用抗 CD16 抗体治疗的 HAM 患者的 PBMC 完全消除了 HAM 中的 NK-T 细胞的抗 HTLV-I 免疫监视。相反，抗CD56和CD57抗体没有表现出这种抑制作用(6)NK-T细胞没有表现出针对HTLV-I感染细胞的任何显着的细胞毒性。在 NK-T 细胞中未检测到 ADCC 效应活性受损可能归因于某些体液因子（例如本研究中的细胞因子）的免疫调节作用。需要效应子活性来开发针对人类逆转录病毒的治疗有效的免疫监视。