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获得性免疫缺陷综合征(AIDS)效应细胞通过抗体依赖性细胞毒性(ADCC)介导对包被有人类免疫缺陷病毒(HIV)的CD4 + T淋巴细胞的破坏。

Antibody-dependent cellular cytotoxicity (ADCC)-mediated destruction of human immunodeficiency virus (HIV)-coated CD4+ T lymphocytes by acquired immunodeficiency syndrome (AIDS) effector cells.

作者信息

Katz J D, Nishanian P, Mitsuyasu R, Bonavida B

机构信息

Department of Microbiology & Immunology, UCLA School of Medicine 90024.

出版信息

J Clin Immunol. 1988 Nov;8(6):453-8. doi: 10.1007/BF00916950.

DOI:10.1007/BF00916950
PMID:2975670
Abstract

The acquired immunodeficiency syndrome (AIDS) is defined in clinical terms by the development of Kaposi's sarcoma and/or severe opportunistic infections in persons without predisposing conditions. A hallmark of the syndrome has been a decrease in the number of CD4+ T helper cells. The reduction in the frequency of the CD4+ lymphocytes has been postulated to be primarily the result of human immunodeficiency virus (HIV) tropism and cytophathogenicity for the T-cell subset. Yet only a small percentage of cells in actually infected with HIV. Recently, we provided evidence indicating that AIDS patients' natural killer cells can mediate normal levels of antibody-dependent cellular cytotoxicity (ADCC) despite exhibiting a defect in natural killer (NK) effector function (J Immunol 139:55, 1987). This finding prompted us to investigate whether AIDS patients' effector cells could mediate ADCC against circulating CD4+ T cells infected with or expressing HIV antigen. The findings reported herein demonstrate that AIDS effector cells can mediate lysis of CEM (CD4+ T-cell line) coated with HIV protein in the presence of HIV-specific antibody. Lysis was specific, as non-HIV-coated CEM or the addition of HIV-negative serum resulted in no lysis. We then examined HIV-coated peripheral blood-derived CD4+ T lymphocytes as targets in ADCC. We demonstrate that in the presence of HIV-specific antibody, HIV-coated CD4+ T lymphocytes serve as targets for ADCC by AIDS effector cells. The lytic activity obtained with AIDS effector cells was comparable to that obtained with normal effector cells.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

获得性免疫缺陷综合征(艾滋病)在临床上定义为在无易感因素的人群中出现卡波西肉瘤和/或严重机会性感染。该综合征的一个标志是CD4 + T辅助细胞数量减少。CD4 +淋巴细胞频率的降低被认为主要是人类免疫缺陷病毒(HIV)对T细胞亚群的嗜性和细胞致病性的结果。然而,实际上只有一小部分细胞感染了HIV。最近,我们提供的证据表明,艾滋病患者的自然杀伤细胞尽管在自然杀伤(NK)效应功能方面存在缺陷,但仍能介导正常水平的抗体依赖性细胞毒性(ADCC)(《免疫学杂志》139:55,1987)。这一发现促使我们研究艾滋病患者的效应细胞是否能介导针对感染或表达HIV抗原的循环CD4 + T细胞的ADCC。本文报道的研究结果表明,在存在HIV特异性抗体的情况下,艾滋病效应细胞可以介导对包被有HIV蛋白的CEM(CD4 + T细胞系)的裂解。裂解具有特异性,因为未包被HIV的CEM或加入HIV阴性血清均未导致裂解。然后,我们将包被有HIV的外周血来源的CD4 + T淋巴细胞作为ADCC的靶标进行检测。我们证明,在存在HIV特异性抗体的情况下,包被有HIV的CD4 + T淋巴细胞可作为艾滋病效应细胞ADCC的靶标。艾滋病效应细胞获得的裂解活性与正常效应细胞获得的裂解活性相当。(摘要截短于250字)

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本文引用的文献

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Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS).在获得性免疫缺陷综合征(艾滋病)中分离出人T细胞白血病病毒。
Science. 1983 May 20;220(4599):865-7. doi: 10.1126/science.6601823.
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Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes.淋巴结病相关病毒(LAV)对辅助诱导性T淋巴细胞的选择性嗜性。
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人类胸腺的人类免疫缺陷病毒感染及SCID-hu小鼠胸腺微环境的破坏。
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Serum and effector-cell antibody-dependent cellular cytotoxicity (ADCC) activity remains high during human immunodeficiency virus (HIV) disease progression.在人类免疫缺陷病毒(HIV)疾病进展过程中,血清及效应细胞抗体依赖性细胞毒性(ADCC)活性仍保持较高水平。
J Clin Immunol. 1989 Nov;9(6):454-61. doi: 10.1007/BF00918014.
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Quantitation of antigen-specific immune responses in human immunodeficiency virus (HIV)-infected individuals by limiting dilution analysis.通过有限稀释分析对人类免疫缺陷病毒(HIV)感染个体中的抗原特异性免疫反应进行定量分析。
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既往健康的同性恋男性中的卡氏肺孢子虫肺炎和黏膜念珠菌病:一种新获得性细胞免疫缺陷的证据。
N Engl J Med. 1981 Dec 10;305(24):1425-31. doi: 10.1056/NEJM198112103052401.
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Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).从一名有获得性免疫缺陷综合征(艾滋病)风险的患者体内分离出一种嗜T淋巴细胞逆转录病毒。
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Mechanism of defective NK cell activity in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. I. Defective trigger on NK cells for NKCF production by target cells, and partial restoration by IL 2.获得性免疫缺陷综合征(AIDS)及AIDS相关综合征患者自然杀伤(NK)细胞活性缺陷的机制。I. 靶细胞触发NK细胞产生NK细胞趋化因子(NKCF)存在缺陷,而白细胞介素2(IL 2)可使其部分恢复。
J Immunol. 1986 Aug 15;137(4):1157-63.
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Human T-cell lymphotropic virus IIIB glycoprotein (gp120) bound to CD4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack.人类嗜T细胞病毒IIIB型糖蛋白(gp120)与正常淋巴细胞上的CD4决定簇结合,并由受感染细胞表达,成为免疫攻击的靶标。
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Sera from HTLV-III/LAV antibody-positive individuals mediate antibody-dependent cellular cytotoxicity against HTLV-III/LAV-infected T cells.来自人类嗜T淋巴细胞病毒III型/淋巴腺病相关病毒(HTLV-III/LAV)抗体阳性个体的血清介导针对HTLV-III/LAV感染的T细胞的抗体依赖性细胞毒性。
J Immunol. 1987 Feb 15;138(4):1064-7.