Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1.

Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1.
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DOI:
10.1126/science.2556795
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发表时间:
1989-12
期刊:
影响因子:
56.9
通讯作者:
R. Viscidi;K. Mayur;H. Lederman;A. Frankel
R. Viscidi;K. Mayur;H. Lederman;A. Frankel
中科院分区:
综合性期刊1区
文献类型:
--
作者:
R. Viscidi;K. Mayur;H. Lederman;A. Frankel

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纯化的人类免疫缺陷病毒1型(hiv - 1) Tat蛋白在纳米摩尔浓度下对破伤风类毒素或念珠菌抗原诱导的淋巴细胞增殖的抑制作用为66%至97%。相比之下,在有丝分裂原如植物血凝素或美洲商陆有丝分裂原的作用下,Tat并没有引起淋巴细胞增殖的显著减少。通过氧化Tat的富含半胱氨酸的区域或在试验前与Tat抗体孵育,抑制作用被阻断。合成的Tat肽(残基1至58)也能抑制抗原刺激的增殖。对H9和U937细胞系的实验表明,Tat可以很容易地进入淋巴细胞和单核细胞。Tat对抗原诱导淋巴细胞增殖的特异性抑制与HIV感染者淋巴细胞的抑制效果相似,表明Tat可能直接促进与HIV感染相关的免疫抑制。
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.