Viscidi R P, Mayur K, Lederman H M, Frankel A D
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Science. 1989 Dec 22;246(4937):1606-8. doi: 10.1126/science.2556795.
The purified human immunodeficiency virus type-l (HIV-l) Tat protein inhibited lymphocyte proliferation induced by tetanus toxoid or Candida antigens by 66 to 97% at nanomolar concentrations of Tat. In contrast, Tat did not cause a significant reduction of lymphocyte proliferation in response to mitogens such as phytohemagglutinin or pokeweed mitogen. Inhibition was blocked by oxidation of the cysteine-rich region of Tat or by incubation with an antibody to Tat before the assay. A synthetic Tat peptide (residues 1 to 58) also inhibited antigen-stimulated proliferation. Experiments with H9 and U937 cell lines showed that Tat can easily enter both lymphocytes and monocytes. The specific inhibition of antigen-induced lymphocyte proliferation by Tat mimics the effect seen with lymphocytes from HIV-infected individuals and suggests that Tat might directly contribute to the immunosuppression associated with HIV infection.
纯化的人免疫缺陷病毒1型（HIV-1）Tat蛋白在纳摩尔浓度的Tat下，可将破伤风类毒素或念珠菌抗原诱导的淋巴细胞增殖抑制66%至97%。相比之下，Tat对诸如植物血凝素或商陆有丝分裂原等有丝分裂原诱导的淋巴细胞增殖没有显著降低作用。Tat富含半胱氨酸区域的氧化或在检测前与抗Tat抗体孵育可阻断抑制作用。一种合成的Tat肽（第1至58位氨基酸残基）也抑制抗原刺激的增殖。对H9和U937细胞系的实验表明，Tat可轻易进入淋巴细胞和单核细胞。Tat对抗原诱导的淋巴细胞增殖的特异性抑制类似于在HIV感染个体的淋巴细胞中观察到的效应，提示Tat可能直接导致与HIV感染相关的免疫抑制。
