Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets
Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets
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DOI：
10.1016/s1074-7613(01)00103-0
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发表时间：
2001-03-01
期刊：
影响因子：
32.4
通讯作者：
Locksley, RM
中科院分区：
文献类型：
--
作者：
Grogan, JL;Mohrs, M;Locksley, RM
在Th1或Th2条件下通过TCR/CD28激活的初始CD4(+) T细胞，无论细胞分裂情况如何，都表达典型的细胞因子模式。只有分裂次数少于4次的细胞在相反条件下再次刺激时能够重新表达其他细胞因子。尽管T细胞在数小时内以不依赖Stat4/Stat6的方式转录干扰素 -γ和白细胞介素 - 4，但没有Stat信号时，T - bet和GATA - 3都不能被最佳诱导，并且极化的细胞因子表达不能持续。细胞因子基因在静息T细胞核中与异染色质分离，这与快速表达一致。极化后，大多数沉默的细胞因子等位基因重新定位到异染色质。初始T细胞在极化为分化的效应细胞亚群过程中经历细胞因子激活、定型、沉默和物理稳定的连续阶段。
Naive CD4(+) T cells activated through TCR/CD28 under Th1 or Th2 conditions expressed canonical cytokine patterns irrespective of cell division. Only cells that had divided fewer than four times were capable of reexpressing alternative cytokines when restimulated under opposing conditions. Although T cells transcribed both IFN-gamma and IL-4 within hours in a Stat4-/Stat6-independent manner, neither T-bet nor GATA-3 was induced optimally without Stat signals, and polarized cytokine expression was not sustained. Cytokine genes were positioned apart from heterochromatin in resting T cell nuclei, consistent with rapid expression. After polarization, the majority of silenced cytokine alleles were repositioned to heterochromatin. Naive T cells transit through sequential stages of cytokine activation, commitment, silencing, and physical stabilization during polarization into differentiated effector subsets.