Sandstrom P A, Roberts B, Folks T M, Buttke T M
Department of Microbiology and Immunology, East Carolina University, School of Medicine, Greenville, North Carolina 27858.
AIDS Res Hum Retroviruses. 1993 Nov;9(11):1107-13. doi: 10.1089/aid.1993.9.1107.
A human T cell lineage was used to determine the possible effects of HIV infection on T cell antioxidant status. On inoculation into serum-free culture, 8E5, a constitutive HIV-expressing T cell line, underwent apoptosis whereas cell death was not observed with the uninfected A3.01 or latently HIV-infected 8E5L T cell lines. 8E5 survival was markedly prolonged by supplementing the serum-free medium with either A3.01-conditioned medium, catalase, vitamin E, or 2-mercaptoethanol, but supplementation with ascorbic acid, glutathione, or N-acetylcysteine had no effect. Consistent with their being in a state of oxidative stress, 8E5 cells displayed reduced levels of catalase activity, and were more susceptible to killing by exogenous hydrogen peroxide (H2O2) than A3.01 and 8E5L cells. These results demonstrate an inverse correlation between HIV gene expression and antioxidant status in human T cells. Enhanced cytotoxicity of HIV-infected, antioxidant-deficient CD4 T cells following exposure to H2O2 in lymphoid tissues responding to opportunistic pathogens may contribute to the depletion of CD4 T cells in AIDS.
利用人类T细胞谱系来确定HIV感染对T细胞抗氧化状态的可能影响。在接种到无血清培养基中后,组成型表达HIV的T细胞系8E5发生凋亡,而未感染的A3.01或潜伏感染HIV的8E5L T细胞系未观察到细胞死亡。通过向无血清培养基中添加A3.01条件培养基、过氧化氢酶、维生素E或2-巯基乙醇,8E5的存活时间显著延长,但添加抗坏血酸、谷胱甘肽或N-乙酰半胱氨酸则没有效果。与处于氧化应激状态一致,8E5细胞的过氧化氢酶活性水平降低,并且比A3.01和8E5L细胞更容易被外源性过氧化氢(H2O2)杀伤。这些结果表明人类T细胞中HIV基因表达与抗氧化状态呈负相关。在对机会性病原体作出反应的淋巴组织中,HIV感染的、抗氧化剂缺乏的CD4 T细胞在暴露于H2O2后细胞毒性增强,这可能导致艾滋病中CD4 T细胞的耗竭。