Signals involved in T cell activation. II. Distinct roles of intact accessory cells, phorbol esters, and interleukin 1 in activation and cell cycle progression of resting T lymphocytes.
Signals involved in T cell activation. II. Distinct roles of intact accessory cells, phorbol esters, and interleukin 1 in activation and cell cycle progression of resting T lymphocytes.
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参与 T 细胞激活的信号。
DOI：
10.4049/jimmunol.136.10.3588
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发表时间：
1986
影响因子：
4.4
通讯作者：
P. Lipsky
中科院分区：
文献类型：
--
作者：
L. Davis;P. Lipsky
研究了静息豚鼠T细胞有丝分裂原诱导激活的起始信号。植物血凝素（PHA）和4 - β -phorbol 12-肉豆蔻酸13-醋酸酯（PMA）的结合刺激辅助细胞（AC）缺失的T细胞在高密度培养下合成DNA，但使用低密度培养表明，即使在PMA、白细胞介素1 （IL 1）或白细胞介素2 （IL 2）存在的情况下，完整的AC对于PHA刺激的T细胞DNA合成也是绝对必要的。相比之下，ac耗尽的T细胞能够对钙离子载体、离子霉素和PMA的组合产生反应，而不管细胞密度如何。吖啶橙染色细胞周期分析表明，在没有AC的情况下，PHA和离子霉素都不能激活静息T细胞。在没有AC的情况下，PMA支持大多数离子霉素刺激的T细胞进入细胞周期并进入DNA合成阶段，但只允许少数pha触发的T细胞进入细胞周期的初始阶段（G1a），其特征是细胞RNA含量适度增加。尽管PMA允许一些pha刺激的T细胞进入细胞周期，但大多数T细胞需要完整的AC进入G1，并且所有T细胞都需要完整的AC进入G1并合成最大量的RNA。没有完整AC的pha刺激细胞无法进入S期。在含有完整AC的pha刺激培养中，PMA增加了进入细胞周期的细胞数量，提高了它们进入DNA合成期的速度。在PMA存在或不存在的情况下，IL - 1也增强了pha刺激的ac依赖性T细胞DNA合成，但似乎在第一个细胞周期的后期最活跃，增加了进入细胞周期S期的活化细胞的数量。这些结果支持完整的AC、IL 1和pma样信号在有丝分裂原刺激的T细胞通过第一轮细胞周期的进展中发挥不同作用的结论。
The signals involved in the initiation of mitogen-induced activation of resting guinea pig T cells were examined. The combination of phytohemagglutinin (PHA) and 4 beta-phorbol 12-myristate 13-acetate (PMA) stimulated DNA synthesis by accessory cell (AC)-depleted T cells cultured at high density, but the use of low density cultures indicated that intact AC were absolutely necessary for PHA-stimulated T cell DNA synthesis even in the presence of PMA, interleukin 1 (IL 1), or interleukin 2 (IL 2). In contrast, AC-depleted T cells were able to respond to the combination of the calcium ionophore, ionomycin, and PMA regardless of the cell density at which they were cultured. Cell cycle analysis by acridine orange staining indicated that neither PHA nor ionomycin, in the absence of AC, activated resting T cells. PMA in the absence of all AC, supported cell cycle entry and progression to the DNA synthetic phase of the majority of ionomycin-stimulated T cells, but permitted only a small number of PHA-triggered T cells to enter the initial stage of the cell cycle (G1a) characterized by a modest increase in cellular RNA content. Although PMA permitted some PHA-stimulated T cells to enter the cell cycle, most required intact AC to enter G1, and all required intact AC to progress through G1 and synthesize maximal amounts of RNA. No PHA-stimulated cells reached the S phase without intact AC. In PHA-stimulated cultures containing intact AC, PMA increased the number of cells entering the cell cycle and increased the rate of their progress to the DNA synthetic phase. IL 1 also augmented PHA-stimulated AC-dependent T cell DNA synthesis in the presence or absence of PMA, but appeared to be most active during the later stage of the first cell cycle, augmenting the number of activated cells that entered the S phase of the cell cycle. These results support the conclusion that intact AC, IL 1, and a PMA-like signal play distinct roles in the progression of mitogen-stimulated T cells through the first round of the cell cycle.