CD4+ blood lymphocytes are rapidly killed in vitro by contact with autologous human immunodeficiency virus-infected cells.

CD4+ blood lymphocytes are rapidly killed in vitro by contact with autologous human immunodeficiency virus-infected cells.
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DOI:
10.1073/pnas.92.16.7312
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发表时间:
1995-08
影响因子:
11.1
通讯作者:
B. Nardelli;C. Gonzalez;M. Schechter;F. Valentine
B. Nardelli;C. Gonzalez;M. Schechter;F. Valentine
中科院分区:
综合性期刊1区
文献类型:
--
作者:
B. Nardelli;C. Gonzalez;M. Schechter;F. Valentine

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我们已经研究了人类免疫缺陷病毒(HIV)感染的细胞杀死未感染的CD 4+淋巴细胞的能力。将感染的外周血单个核细胞与自体51 Cr标记的未感染细胞共培养。短暂孵育后,观察到正常CD 4表达目标群体迅速死亡。在合胞体形成之前或在正常靶细胞中建立生产性病毒感染之前,血液CD 4+淋巴细胞发生死亡。细胞溶解不能诱导游离病毒,依赖于gp 120-CD 4结合,并发生在休息,以及活化,淋巴细胞。CD 8+细胞不参与这种现象,因为HIV感染的CEMT 4细胞(CD 4+,CD 8-细胞)介导未感染靶细胞的细胞溶解。相互同位素标记实验表明,受感染的CEMT 4细胞不会与其靶细胞平行死亡。未感染的靶细胞表现出DNA片段化,随后释放51 Cr标记。因此,在HIV患者中,受感染的淋巴细胞可能通过触发凋亡性死亡而导致大量未感染的CD 4+细胞的消耗,而实际上并没有感染它们。
We have investigated the ability of human immunodeficiency virus (HIV)-infected cells to kill uninfected CD4+ lymphocytes. Infected peripheral blood mononuclear cells were cocultured with autologous 51Cr-labeled uninfected cells. Rapid death of the normal CD4-expressing target population was observed following a brief incubation. Death of blood CD4+ lymphocytes occurred before syncytium formation could be detected or productive viral infection established in the normal target cells. Cytolysis could not be induced by free virus, was dependent on gp120-CD4 binding, and occurred in resting, as well as activated, lymphocytes. CD8+ cells were not involved in this phenomenon, since HIV-infected CEMT4 cells (CD4+, CD8- cells) mediated the cytolysis of uninfected targets. Reciprocal isotope-labeling experiments demonstrated that infected CEMT4 cells did not die in parallel with their targets. The uninfected target cells manifested DNA fragmentation, followed by the release of the 51Cr label. Thus, in HIV patients, infected lymphocytes may cause the depletion of the much larger population of uninfected CD4+ cells without actually infecting them, by triggering an apoptotic death.