Generation of T Follicular Helper Cells Is Mediated by Interleukin-21 but Independent of T Helper 1, 2, or 17 Cell Lineages

Academic Article

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 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. © 2008 Elsevier Inc. All rights reserved. +
  • Published In

  • Immunity  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 9332388
  • Author List

  • Nurieva RI; Chung Y; Hwang D; Yang XO; Kang HS; Ma L; Wang YH; Watowich SS; Jetten AM; Tian Q
  • Start Page

  • 138
  • End Page

  • 149
  • Volume

  • 29
  • Issue

  • 1