Cottrez F, Manca F, Dalgleish A G, Arenzana-Seisdedos F, Capron A, Groux H
Unité mixte Institut National de la Santé et de la Recherche Médicale U167-CNRS 624, Institut Pasteur, Lille, France.
J Clin Invest. 1997 Jan 15;99(2):257-66. doi: 10.1172/JCI119154.
The study of the pathology of HIV-1 infection in chimpanzees supports the idea of the crucial role of HIV-infected monocytes in the pathogenesis of AIDS, although viral mechanisms that lead to T cell dysfunction and deletion during HIV infection are still unclear. We show here that HIV-1-infected antigen-presenting monocytes (APCs) are able to prime in vitro non-HIV-infected antigen-specific CD4+ T cell lines or peripheral blood CD4+ T cells to undergo apoptosis after antigen-specific restimulation. The priming of T cells for apoptosis occurs in the absence of HIV replication in the T cells. Priming for apoptosis required two concomitant signals present on the same APC, an antigenic stimulus and a second signal provided by the HIV gp120 protein as demonstrated by the use as APCs of EBV-LCLs infected with different recombinant deleted proviruses or transfected with different HIV proteins. These results provide a mechanism for the priming for apoptosis of T cells in HIV-infected patients, implicating a role for HIV-infected APCs in the induction of T cell dysfunction and depletion in AIDS.
对黑猩猩体内HIV-1感染病理学的研究支持了HIV感染的单核细胞在艾滋病发病机制中起关键作用这一观点，尽管导致HIV感染期间T细胞功能障碍和缺失的病毒机制仍不清楚。我们在此表明，HIV-1感染的抗原呈递单核细胞（APC）能够在体外使未感染HIV的抗原特异性CD4+ T细胞系或外周血CD4+ T细胞在抗原特异性再刺激后发生凋亡。T细胞凋亡的启动发生在T细胞中无HIV复制的情况下。凋亡启动需要同一APC上存在的两个伴随信号，一个是抗原刺激，另一个是HIV gp120蛋白提供的第二信号，这一点通过使用感染不同重组缺失前病毒或转染不同HIV蛋白的EBV-LCL作为APC得到了证明。这些结果为HIV感染患者T细胞凋亡启动提供了一种机制，提示HIV感染的APC在艾滋病中T细胞功能障碍和耗竭的诱导中起作用。
