Mitogenic CD2 monoclonal antibody pairs predispose peripheral T cells to undergo apoptosis on interaction with a third CD2 monoclonal antibody.

Mitogenic CD2 monoclonal antibody pairs predispose peripheral T cells to undergo apoptosis on interaction with a third CD2 monoclonal antibody.
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促有丝分裂 CD2 单克隆抗体对使外周 T 细胞在与第三个 CD2 单克隆抗体相互作用时容易发生凋亡。

DOI:
10.4049/jimmunol.152.10.4861
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发表时间:
1994
影响因子:
4.4
通讯作者:
A. Senik
A. Senik
中科院分区:
医学2区
文献类型:
--
作者:
M. Rouleau;B. Mollereau;A. Bernard;D. Métivier;M. Rosenthal;B. Charpentier;A. Senik

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当用促有丝分裂GT 2 + T11(1)CD 2 mAb对和IL-2刺激几天时,静息T细胞被诱导增殖,但向培养物中引入第三种CD 2 mAb导致40 - 60%的细胞凋亡性细胞死亡。死亡信号在T细胞进入细胞周期时是活跃的,而不引起明显的细胞周期阻滞,也不区分G1期和S期。放线菌酮或放线菌素D不能阻止细胞凋亡,这表明死亡程序已经在等待适当信号的预活化细胞中表达。针对各种细胞表面分子的一系列Ab不能触发细胞凋亡(CD 3 mAb除外),而大多数检测的CD 2 mAb具有活性,前提是第三种CD 2 mAb识别与GT 2和T11不同的表位(1)。CD 2分子的单纯聚集似乎不是细胞凋亡的触发信号,因为将细胞结合的GT 2 + T11(1)与抗小鼠IgG的Ab交联没有效果,这表明第三种CD 2 mAb对CD 2分子施加了构象变化。在IL-2存在下进行的刺激使CD 45 R 0+和CD 45 RA + T细胞易于凋亡,而在IL-4存在下进行的刺激仅使CD 45 RA + T细胞经历该过程。单核细胞和CD 2通路的有效辅信号不能阻止CD 2诱导的细胞凋亡。因此,成熟T细胞的CD 2分子通过识别不同表位的两种和三种CD 2 mAb的连续接合可以在短期培养物中提供增殖和凋亡的信号,这取决于细胞的活化状态。
When stimulated for a few days with the mitogenic GT2 + T11(1) CD2 mAb pair and IL-2, resting T cells were induced to proliferate but the introduction into the cultures of a third CD2 mAb resulted in apoptotic cell death of 40 to 60% of the cells. The death signal was active on T cells entered the cell cycle without causing an apparent cell cycle block and without discriminating between the G1 and S phases. Apoptosis was not prevented by cycloheximide or actinomycin D, indicating that the death program was already expressed in preactivated cells awaiting an appropriate signal. A series of Abs, directed at various cell surface molecules, were unable to trigger apoptosis (except CD3 mAb), whereas most of the CD2 mAb tested were active, provided the third CD2 mAb was recognizing an epitope different from GT2 and T11(1). Mere aggregation of CD2 molecules did not seem to be the triggering signal of apoptosis, because cross-linking cell-bound GT2 + T11(1) with an Ab to mouse IgG had no effect, suggesting that a conformational change was imposed on CD2 molecules by the third CD2 mAb. Stimulation performed in the presence of IL-2 predisposed both CD45R0+ and CD45RA+ T cells to apoptosis, whereas stimulation in the presence of IL-4 primed only CD45RA+ T cells to undergo this process. Monocytes and potent co-signals of the CD2 pathway were unable to prevent CD2-induced apoptosis. Thus, successive engagements of the CD2 molecule of mature T cells by two and three CD2 mAbs recognizing distinct epitopes can provide in short term cultures signals for proliferation and apoptosis, depending on the activation state of the cells.
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