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.

抗体依赖性细胞介导的细胞毒性（ADCC）在HTLV-I相关的骨髓病（HAM）中受损。免疫监视的这种缺陷可能会使HAM中人类T淋巴细胞病毒（HTLV-I）的复制增加。这是我们研究了影响HAM中抗HTLV-I ADCC受损的因素。（1）将HAM中的外周血单核细胞（PBMC）和对照组与细胞因子（例如白介素-2，Interferon-Alpha和Interferon-Gamma）预孵育，然后在ADCC分析中使用。在所有对照组中，ADCC的活动都得到了增加，但是在一半以上的HAM患者中，它们进一步损害了它们。（2）HAM的蛋白G处理的血清未显示任何抗HTLV-I ADCC活性，表明ADCC抗体是LGG类别的。（3）通过反义方法抑制HTLV-I税收表达不会改变抗HTLV-I ADCC活性。（4）CD3+CD16+细胞子集显示了总ADCC效应子活性的1/3〜1/4。我们先前报道了HAM中的CD56+细胞子集（NK-T细胞标记物）的降低。我们研究了HAM中NK-T细胞的抗HTLV-I免疫监视。（5）用抗CD16抗体治疗的HAM患者的PBMC完全消除了抗HTLV-I ADCC活性。相反，抗CD56和CD57抗体没有显示出这种抑制作用。（6）NK-T细胞对HTLV-I感染细胞没有任何明显的细胞毒性。（7）在NK-T细胞中未检测到HTLV-I基因组。 ADCC效应活性受损可能归因于某些体液因子的免疫调节作用，例如本研究中的细胞因子。需要急剧寻找识别因素来增加ADCC效应活性的因素，以开发针对人类逆转录病毒的治疗有效的免疫护理。