Monocytes are required to prime peripheral blood T cells to undergo apoptosis.

Monocytes are required to prime peripheral blood T cells to undergo apoptosis.
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单核细胞需要启动外周血 T 细胞进行凋亡。

DOI:
10.1073/pnas.92.5.1525
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发表时间:
1995
影响因子:
11.1
通讯作者:
Schlossman,SF
Schlossman,SF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wu,MX;Daley,JF;Rasmussen,RA;Schlossman,SF

文献摘要

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新鲜分离的人外周血T(PBT)细胞在很大程度上对抗CD 3单克隆抗体、离子霉素或佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)的凋亡作用具有抗性。然而,我们在这里证明,PBT细胞,包括CD 4+和CD 8+细胞群体,可以很容易地诱导进行细胞凋亡时,与自体或同种异体单核细胞(Mo)在PMA含培养基中共培养。PBT细胞与Mo以1:1的比例孵育18小时导致最大水平(80%)的凋亡性细胞死亡。Mo使PBT细胞在含PMA的培养基中发生凋亡的机制似乎取决于Mo和PBT细胞之间的细胞-细胞接触或紧密接近,而不仅仅是通过可溶性介质。证明了Mo在用PMA处理后获得引发PBT细胞凋亡的能力,并且处理的Mo即使在用甲醛固定后也保持这种能力。还发现,一旦PBT细胞通过与PMA预处理的Mo孵育而引发凋亡,引发的PBT细胞不仅对PMA触发的凋亡敏感,而且对离子霉素或T细胞表面分子如CD 4和CD 3的单克隆抗体交联也敏感。有趣的是,CD 4 + T细胞的细胞凋亡的程度通过交联的CD 4分子的gp 120,抗gp 120,和山羊抗小鼠IgG的组合是显着更大的PMA处理的钼引发的T细胞比未引发的T细胞。总之,这些研究结果揭示了一个重要的作用,辅助细胞在引发静息PBT细胞凋亡,并建议一个可能的Mo依赖性机制,T细胞可能成为引发人类免疫缺陷病毒感染的无症状个体的凋亡。
Freshly isolated, human peripheral blood T (PBT) cells are largely resistant to the apoptotic effects of anti-CD3 monoclonal antibody, ionomycin, or phorbol 12-myristate 13-acetate (PMA). We demonstrate here, however, that PBT cells, including both CD4+ and CD8+ cell populations, can be readily induced to undergo apoptosis when cocultured with either autologous or allogeneic monocytes (Mo) in PMA-containing medium. Incubation of PBT cells with Mo at a ratio of 1:1 for 18 hr resulted in maximal levels (80%) of apoptotic cell death. The mechanism whereby Mo enable PBT cells to undergo apoptosis in PMA-containing medium appeared to depend on cell-cell contact or close proximity between Mo and PBT cells rather than solely via soluble mediators. It was demonstrated that Mo acquire the ability to prime PBT cells for apoptosis after treatment with PMA and that treated Mo maintain this ability even after fixation with formaldehyde. It was also found that once PBT cells became primed for apoptosis by incubation with PMA-pretreated Mo, the primed PBT cells were susceptible to apoptosis triggered not only by PMA but also by either ionomycin or by monoclonal antibody crosslinking of T-cell surface molecules such as CD4 and CD3. Interestingly, the degree of apoptosis of CD4+ T cells by crosslinking of CD4 molecules via a combination of gp120, anti-gp120, and goat anti-mouse IgG was significantly greater for T cells primed with PMA-treated Mo than for unprimed T cells. Together, these findings reveal an important role for accessory cells in priming resting PBT cells for apoptosis and suggest a possible Mo-dependent mechanism by which T cells may become primed for apoptosis in human immunodeficiency virus-infected asymptomatic individuals.