Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets - PubMed (original) (raw)
Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets
J L Grogan et al. Immunity. 2001 Mar.
Free article
Abstract
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.
Similar articles
- Activation of STAT proteins and cytokine genes in human Th1 and Th2 cells generated in the absence of IL-12 and IL-4.
Moriggl R, Kristofic C, Kinzel B, Volarevic S, Groner B, Brinkmann V. Moriggl R, et al. J Immunol. 1998 Apr 1;160(7):3385-92. J Immunol. 1998. PMID: 9531298 - Cytokine transcriptional events during helper T cell subset differentiation.
Lederer JA, Perez VL, DesRoches L, Kim SM, Abbas AK, Lichtman AH. Lederer JA, et al. J Exp Med. 1996 Aug 1;184(2):397-406. doi: 10.1084/jem.184.2.397. J Exp Med. 1996. PMID: 8760793 Free PMC article. - GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet.
Usui T, Nishikomori R, Kitani A, Strober W. Usui T, et al. Immunity. 2003 Mar;18(3):415-28. doi: 10.1016/s1074-7613(03)00057-8. Immunity. 2003. PMID: 12648458 - T helper subset development: roles of instruction, selection, and transcription.
Farrar JD, Asnagli H, Murphy KM. Farrar JD, et al. J Clin Invest. 2002 Feb;109(4):431-5. doi: 10.1172/JCI15093. J Clin Invest. 2002. PMID: 11854312 Free PMC article. Review. No abstract available. - The function role of GATA-3 in Th1 and Th2 differentiation.
Zhou M, Ouyang W. Zhou M, et al. Immunol Res. 2003;28(1):25-37. doi: 10.1385/IR:28:1:25. Immunol Res. 2003. PMID: 12947222 Review.
Cited by
- Regulators of chromatin state and transcription in CD4 T-cell polarization.
Josefowicz SZ. Josefowicz SZ. Immunology. 2013 Jul;139(3):299-308. doi: 10.1111/imm.12115. Immunology. 2013. PMID: 23590627 Free PMC article. Review. - T helper type 1-specific Brg1 recruitment and remodeling of nucleosomes positioned at the IFN-gamma promoter are Stat4 dependent.
Zhang F, Boothby M. Zhang F, et al. J Exp Med. 2006 Jun 12;203(6):1493-505. doi: 10.1084/jem.20060066. Epub 2006 May 22. J Exp Med. 2006. PMID: 16717115 Free PMC article. - T-bet expression is upregulated in active Behçet's disease.
Li B, Yang P, Zhou H, Zhang Z, Xie C, Lin X, Huang X, Kijlstra A. Li B, et al. Br J Ophthalmol. 2003 Oct;87(10):1264-7. doi: 10.1136/bjo.87.10.1264. Br J Ophthalmol. 2003. PMID: 14507763 Free PMC article. - Evidence inconsistent with a negative influence of T helper 2 cells on protection afforded by a dominant T helper 1 response against Mycobacterium tuberculosis lung infection in mice.
Jung YJ, LaCourse R, Ryan L, North RJ. Jung YJ, et al. Infect Immun. 2002 Nov;70(11):6436-43. doi: 10.1128/IAI.70.11.6436-6443.2002. Infect Immun. 2002. PMID: 12379724 Free PMC article. - Chronic inflammation and asthma.
Murdoch JR, Lloyd CM. Murdoch JR, et al. Mutat Res. 2010 Aug 7;690(1-2):24-39. doi: 10.1016/j.mrfmmm.2009.09.005. Epub 2009 Sep 19. Mutat Res. 2010. PMID: 19769993 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous