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

First Author  Grogan JL Year  2001
Journal  Immunity Volume  14
Issue  3 Pages  205-15
PubMed ID  11290331 Mgi Jnum  J:68346
Mgi Id  MGI:1932590 Doi  10.1016/s1074-7613(01)00103-0
Citation  Grogan JL, et al. (2001) Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14(3):205-15
abstractText  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.
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