CD8+ T-cell-mediated non-cytolytic suppression of human immuno-deficiency viruses.

C Vella, R S Daniels
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引用次数: 13

Abstract

Major histocompatibility (MHC)-restricted cytotoxic T-lymphocytes (CTL) kill human immunodeficiency virus (HIV)-infected cells. In addition, activated CD8(+) T-lymphocytes from HIV-infected individuals suppress virus replication in vitro by producing antiviral factor (CAF). The effector mechanism(s) of CAF involves modulation of HIV gene transcription, is non-cytolytic and mediated in part by soluble antiviral factors. Initially, CAF activity was shown to be more vigorous in activated CD8(+) cells and cell free supernatants (SNs) from asymptomatic individuals compared to those with AIDS, suggesting a protective role in vivo. CAF-mediated suppression is also evident in animal models of immunodeficiency virus infection. Several soluble molecules that contribute to non-cytolytic virus suppression have been characterised, including alpha- and beta-chemokines and interleukin-16 (IL-16), but these are distinct from CAF. Two agents possessing certain CAF-like characteristics, modified antithrombin 111 (AT111) and the human alpha-defensins, have been described but their antiviral mechanisms are not fully understood. CAF-secretion may not be virus-specific as similar activity is found in activated CD8(+) cells/SNs from humans and chimpanzees seronegative for HIV-1. Recent data indicates that the secretion of CAF is MHC-restricted and both cytolytic and non-cytolytic mechanisms are mediated by CTL. If the latter is correct, a single appropriate stimulus could be used to enhance both effector mechanisms in vivo. This paper reviews research aimed at characterising HIV-suppressive factors and raises other questions that must be considered for the development of prophylactic and therapeutic strategies leading to the safe and effective control of HIV.

CD8+ t细胞介导的人免疫缺陷病毒的非细胞溶解性抑制。
主要组织相容性(MHC)限制细胞毒性t淋巴细胞(CTL)杀死人类免疫缺陷病毒(HIV)感染的细胞。此外,来自hiv感染者的活化CD8(+) t淋巴细胞通过产生抗病毒因子(CAF)在体外抑制病毒复制。CAF的作用机制涉及对HIV基因转录的调节,非细胞溶解性,部分由可溶性抗病毒因子介导。最初,与艾滋病患者相比,CAF在无症状个体活化的CD8(+)细胞和无细胞上清液(SNs)中的活性更强,这表明CAF在体内具有保护作用。cafa介导的抑制在免疫缺陷病毒感染的动物模型中也很明显。一些有助于非溶细胞病毒抑制的可溶性分子已经被表征,包括α和β趋化因子和白细胞介素-16 (IL-16),但这些与CAF不同。两种具有某些类似caf1特性的药物,修饰抗凝血酶111 (AT111)和人α -防御素,已经被描述,但它们的抗病毒机制尚未完全了解。caf的分泌可能不是病毒特异性的,因为在HIV-1血清阴性的人类和黑猩猩的活化CD8(+)细胞/SNs中发现了类似的活性。最近的数据表明,CAF的分泌受mhc限制,细胞溶解和非细胞溶解机制均由CTL介导。如果后者是正确的,一个单一的适当的刺激可以用来增强体内的两种效应机制。本文综述了旨在表征HIV抑制因子的研究,并提出了其他必须考虑的问题,以制定预防和治疗策略,从而安全有效地控制HIV。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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