Collette Y, Chang H L, Cerdan C, Chambost H, Algarte M, Mawas C, Imbert J, Burny A, Olive D
Institut National de la Santé et de la Recherche Médicale U-119/Institut Paoli Calmette, Marseille, France.
J Immunol. 1996 Jan 1;156(1):360-70.
HIV-1 infection is associated with a progressive and functional decline in the CD4+ lymphoid Th1 subset. Here, we propose that the HIV nef gene product may function as a specific regulator of Th1 cytokine production. By use of a T cell-specific inducible expression system, we show that upon T cell activation, induced nef expression down-regulated both IL-2 and IFN-gamma production in a dose-dependent manner, whereas IL-4, IL-9, IL-13, IL-8, and TNF-alpha production remained unaffected. In addition to this, independent transfected clones expressing various nef genes, including nef sequences amplified directly from an HIV-1 primary clinical isolate, displayed a similar pattern of cytokine expression. The specific Th1 impairment induced by nef, therefore, seems to be an important and conserved feature of HIV-1 infection and may represent a significant function of this viral gene in AIDS pathogenesis.
HIV-1感染与CD4+淋巴细胞Th1亚群的渐进性和功能性衰退相关。在此，我们提出HIV nef基因产物可能作为Th1细胞因子产生的特异性调节因子发挥作用。通过使用T细胞特异性诱导表达系统，我们发现，在T细胞激活后，诱导的nef表达以剂量依赖的方式下调IL-2和IFN-γ的产生，而IL-4、IL-9、IL-13、IL-8和TNF-α的产生不受影响。除此之外，表达各种nef基因的独立转染克隆，包括直接从HIV-1原发性临床分离株扩增的nef序列，显示出类似的细胞因子表达模式。因此，nef诱导的特异性Th1损伤似乎是HIV-1感染的一个重要且保守的特征，可能代表了该病毒基因在艾滋病发病机制中的一项重要功能。
