Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets

被引:409
作者
Grogan, JL
Mohrs, M
Harmon, B
Lacy, DA
Sedat, JW
Locksley, RM [1 ]
机构
[1] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Microbiol, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Dept Immunol, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA
[6] Univ Calif San Francisco, Dept Biophys, San Francisco, CA 94143 USA
关键词
D O I
10.1016/S1074-7613(01)00103-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:205 / 215
页数:11
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