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Nurieva, Roza I.,Chung, Yeonseok,Hwang, Daehee,Yang, Xuexian O.,Kang, Hong Soon,Ma, Li,Wang, Yi-hong,Watowich, Stephanie S.,Jetten, Anton M.,Tian, Qiang,Dong, Chen Elsevier 2008 Immunity Vol.29 No.1
<P><B>Summary</B></P><P>After activation, CD4<SUP>+</SUP> 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 β (TGF-β) or Th17-specific orphan nuclear receptors RORα and RORγ in vivo. Finally, naive T cells activated in vitro in the presence of IL-21 but not TGF-β 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.</P>