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

HTLV-I相关性脊髓病(HAM)患者的抗体依赖细胞介导的细胞毒作用(ADCC)受损。免疫监测的这一缺陷可能会增加HAM中人类T淋巴细胞嗜T细胞病毒I型(HTLV-I)的复制。因此，我们研究了影响火腿抗HTLV-I ADCC受损的因素。(1)HAM组和对照组外周血单个核细胞(PBMC)与细胞因子IL-2、干扰素-α、干扰素-γ预先孵育后用于ADCC检测。ADCC活性在所有对照组均增强，但超过一半的HAM患者ADCC活性进一步受损。(2)HAM经G蛋白处理后的血清未显示抗HTLV-I ADCC活性，表明ADCC抗体为LGG类。(3)用反义方法抑制HTLV-I Tax的表达不改变其抗HTLV-I ADCC的活性。(4)CD3+CD16+细胞亚群占ADCC总效应的1/3~1/4。我们之前报道了HAM患者CD56+细胞亚群的减少，CD56+细胞亚群是一种NK-T细胞标志。我们研究了火腿NK-T细胞抗HTLV-I的免疫监视作用。(5)抗CD16抗体治疗的HAM患者PBMC可完全消除抗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感染细胞无明显杀伤作用。(7)NK-T细胞中未检测到HTLV-I基因。ADCC效应器活性降低可能与某些体液因子的免疫调节作用有关，如本研究中的细胞因子。需要积极寻找增强ADCC效应器活性的因素，以开发针对人类逆转录病毒的治疗有效的免疫监控。

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.