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Immunity. 2008 Jul 18;29(1):138-49. doi: 10.1016/j.immuni.2008.05.009. Epub 2008 Jul 3.

Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages.

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1
Department of Immunology, University of Texas MD Anderson Cancer Center and Graduate School of Biomedical Sciences, Houston, TX 77030, USA. rnurieva@mdanderson.org

Abstract

After activation, CD4(+) helper T (Th) cells differentiate into distinct effector subsets. Although chemokine (C-X-C motif) receptor 5-expressing T follicular helper (Tfh) cells are important in humoral immunity, their developmental regulation is unclear. Here we show that Tfh cells had a distinct gene expression profile and developed in vivo independently of the Th1 or Th2 cell lineages. Tfh cell generation was regulated by ICOS ligand (ICOSL) expressed on B cells and was dependent on interleukin-21 (IL-21), IL-6, and signal transducer and activator of transcription 3 (STAT3). However, unlike Th17 cells, differentiation of Tfh cells did not require transforming growth factor beta (TGF-beta) or Th17-specific orphan nuclear receptors RORalpha and RORgamma in vivo. Finally, naive T cells activated in vitro in the presence of IL-21 but not TGF-beta signaling preferentially acquired Tfh gene expression and promoted germinal-center reactions in vivo. This study thus demonstrates that Tfh is a distinct Th cell lineage.

PMID:
18599325
PMCID:
PMC2556461
DOI:
10.1016/j.immuni.2008.05.009
[Indexed for MEDLINE]
Free PMC Article

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