Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals.
Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals.
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DOI：
10.1084/jem.175.2.331
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发表时间：
1992-02-01
期刊：
影响因子：
--
通讯作者：
Ameisen JC
中科院分区：
文献类型：
--
作者：
Groux H;Torpier G;Monté D;Mouton Y;Capron A;Ameisen JC
在未成熟的胸腺细胞中，T 细胞抗原受体 (TCR) 动员导致活跃的 T 细胞自杀过程，即细胞凋亡，该过程参与 T 细胞库的选择。我们提出，在成熟 CD4+ T 细胞群中不恰当地诱导这种细胞死亡程序可以解释人类免疫缺陷病毒 (HIV) 感染个体的早期定性和晚期定量 CD4+ T 淋巴细胞缺陷（Ameisen, J.C., and A. Capron. 1991.Immunol.Today.4:102）。在这里，我们报道了来自 59 名临床无症状 HIV 感染者的 CD4+ T 细胞在体外增殖至主要组织相容性复合物 II 类依赖性超抗原和美洲商陆有丝分裂原 (PWM) 动员 TCR 的选择性失败是由于活跃的 CD4+ T 细胞死亡过程，具有细胞凋亡的生化和超微结构特征。激活诱导的细胞死亡仅发生在 HIV 感染者的无症状个体的 CD4+ T 细胞群中，而在 58 名 HIV 血清阴性对照（包括 9 名患有其他急性或慢性传染病的患者）的 T 细胞中未观察到激活诱导的细胞死亡。放线菌酮、环孢菌素 A 和 CD28 单克隆抗体 (mAb) 可防止激活诱导的 CD4+ T 细胞死亡。 CD28 mAb 不仅可以防止细胞凋亡，还可以恢复 T 细胞对刺激的增殖，包括 PWM、超级抗原以及破伤风和流感记忆抗原。这些发现可能对理解获得性免疫缺陷综合征的发病机制和设计具体的治疗策略具有重要意义。
In immature thymocytes, T cell receptor for antigen (TCR) mobilization leads to an active T cell suicide process, apoptosis, which is involved in the selection of the T cell repertoire. We have proposed that inappropriate induction of such a cell death program in the mature CD4+ T cell population could account for both early qualitative and late quantitative CD4+ T lymphocyte defects of human immunodeficiency virus (HIV)-infected individuals (Ameisen, J.C., and A. Capron. 1991. Immunol. Today. 4:102). Here, we report that the selective failure of CD4+ T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate in vitro to TCR mobilization by major histocompatibility complex class II-dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4+ T cell death process, with the biochemical and ultrastructural features of apoptosis. Activation-induced cell death occurred only in the CD4+ T cell population from HIV-infected asymptomatic individuals and was not observed in T cells from any of 58 HIV-seronegative controls, including nine patients with other acute or chronic infectious diseases. Activation-induced CD4+ T cell death was prevented by cycloheximide, cyclosporin A, and a CD28 monoclonal antibody (mAb). The CD28 mAb not only prevented apoptosis but also restored T cell proliferation to stimuli, including PWM, superantigens, and the tetanus and influenza recall antigens. These findings may have implications for the understanding of the pathogenesis of acquired immune deficiency syndrome and for the design of specific therapeutic strategies.
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DOI：
10.1084/jem.172.6.1735
发表时间：
1990-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liu Y;Janeway CA Jr
通讯作者：
Janeway CA Jr
影响因子：
56.9
作者：
FAUCI, AS
通讯作者：
FAUCI, AS
影响因子：
15.9
作者：
CLERICI, M;STOCKS, NI;SHEARER, GM
通讯作者：
SHEARER, GM
影响因子：
56.9
作者：
FRASER, JD;IRVING, BA;WEISS, A
通讯作者：
WEISS, A
影响因子：
3.7
作者：
HOFMANN, B;ODUM, N;SVEJGAARD, A
通讯作者：
SVEJGAARD, A