Differential effects of HIV-1 protease inhibitors on dendritic cell immunophenotype and function.
Differential effects of HIV-1 protease inhibitors on dendritic cell immunophenotype and function.
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DOI：
10.1074/jbc.m105582200
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发表时间：
2001-12-21
影响因子：
4.8
通讯作者：
Wong-Staal, F
中科院分区：
文献类型：
--
作者：
Gruber, A;Wheat, JC;Wong-Staal, F
最近的研究结果表明，人类免疫缺陷病毒(HIV)-1蛋白酶抑制剂被设计为特异性抑制HIV-1的天冬氨酸蛋白酶，但在体外和体内对免疫细胞功能有不同的影响。树突状细胞（DC）是免疫系统的核心角色，表达几种对DC功能很重要的天冬氨酸蛋白酶。在目前的研究中，我们证明了所有HIV-1蛋白酶抑制剂都能影响DC成熟。此外，沙奎那韦对成熟DC的t细胞刺激能力有较强的抑制作用。相比之下，因地那韦对DC诱导的t细胞增殖只有轻微的影响，并允许DC用一种为DC免疫治疗设计的复制能力不足的HIV-1载体有效转导。对DC功能影响很小或没有影响的HIV-1蛋白酶抑制剂可能更适合与HIV/AIDS的免疫治疗联合使用。
Recent findings show that human immunodeficiency virus (HIV)-1 protease inhibitors designed to specifically inhibit the aspartic protease of HIV-1 nonetheless exert various effects on immune cell function in vitro and in vivo. Dendritic cells (DC), central players of the immune system, express several aspartic proteases that are important for DC function. In the present study, we demonstrate that all of the HIV-1 protease inhibitors tested affect DC maturation. In addition, saquinavir had a strong inhibitory effect on the T-cell stimulatory capacity of mature DC. In contrast, indinavir had only a slight effect on DC induced T-cell proliferation and allowed efficient transduction of DC with a replication-incompetent HIV-1 vector designed for DC-based immunotherapy. HIV-1 protease inhibitors that have little or no effect on DC function may be preferable for combination with immunotherapy for HIV/AIDS.