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

作者：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

来源：Immunity, 2008, 29(1): 138-149.

DOI：10.1016/j.immuni.2008.05.009

After activation, CD4(+) helper T (Th) cells differentiate into distinct effector subsets. Although chemokine (C-X-C motif]I 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 0 (TGF-beta) or Th17-specific orphan nuclear receptors ROR alpha and ROR gamma 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.

• 出版日期2008-7-18