Cell division is not a "clock" measuring acquisition of competence to produce IFN-γ or IL-4
Cell division is not a "clock" measuring acquisition of competence to produce IFN-γ or IL-4
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DOI：
10.4049/jimmunol.166.1.112
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发表时间：
2001-01-01
影响因子：
4.4
通讯作者：
Paul, WE
中科院分区：
文献类型：
--
作者：
Ben-Sasson, SZ;Gerstel, R;Paul, WE
初始CD4 T细胞在其同源抗原、抗原提呈细胞（APC）以及适当细胞因子存在的情况下培养时，获得产生干扰素 -γ（IFN -γ）和白细胞介素 - 4（IL - 4）的潜能。在本研究中，我们表明，严格纯化的初始CD4 T细胞产生IFN -γ的定向分化可在不发生细胞分裂的情况下发生。实际上，甚至进入S期也不是必需的。此外，来自Rag2（-/-）背景的T细胞受体转基因小鼠（5CC7小鼠）的CD4以及CD4/CD8胸腺细胞在受到肽段、APC和白细胞介素 - 12刺激时，能够获得产生IFN -γ的能力。这些细胞在不分裂的情况下就可以做到这一点，并且一些细胞在不进入S期的情况下就获得了产生IFN -γ的活性。细胞分裂不仅对于获得产生细胞因子的潜能不是必需的，而且经历相同分裂次数的细胞群根据启动（priming）的持续时间，或者就白细胞介素 - 4而言根据肽段浓度的不同，产生IFN -γ或IL - 4的细胞比例可能会有很大差异。因此，细胞分裂并不是这些细胞因子表达的时钟。与启动条件相关的因素，包括刺激强度、启动持续时间和分裂次数，都各自发挥作用。
Naive CD4 T cells acquire the potential to produce IFN-gamma and IL-4 by culture in the presence of their cognate Ag, APC, and appropriate cytokines. In this study, we show that commitment to IFN-gamma production on the part of rigorously purified naive CD4 T cells can occur without cell division. Indeed, even entry into S phase is not essential, Moreover, both CD4 and CD4/CD8 thymocytes from TCR-transgenic mice (5CC7 mice) on a Rag2(-/-) background can acquire IFN-gamma -producing capacity when stimulated by peptide, APC, and IL-12. These cells can do so without dividing and some acquire IFN-gamma -producing activity without entry into S phase. Not only is cell division not required for acquisition of cytokine-producing potential, cell populations that have undergone the same numbers of divisions can have quite different proportions of IFN-gamma- or IL-4-producing cells, depending on the duration of priming or, in the case of IL-4, on the concentration of peptide. Thus, cell division is not a clock for the expression of these cytokines. Factors associated with priming conditions including strength of stimulation, duration of priming, and number of divisions each play a role.