IL-21 promotes CD4 T cell responses by phosphatidylinositol 3-kinase-dependent upregulation of CD86 on B cells

Kesley Attridge, Rupert Kenefeck, Lukasz Wardzinski, Omar S. Qureshi, Chun Jing Wang, Claire Manzotti, Klaus Okkenhaug, Lucy S.K. Walker

Research output: Contribution to journalArticlepeer-review


The cytokine IL-21 is a potent immune modulator with diverse mechanisms of action on multiple cell types. IL-21 is in clinical use to promote tumor rejection and is an emerging target for neutralization in the setting of autoimmunity. Despite its clinical potential, the biological actions of IL-21 are not yet fully understood and the full range of effects of this pleiotropic cytokine are still being uncovered. In this study, we identify a novel role for IL-21 as an inducer of the costimulatory ligand CD86 on B lymphocytes. CD86 provides critical signals through T cell-expressed CD28 that promote T cell activation in response to Ag engagement. Expression levels of CD86 are tightly regulated in vivo, being actively decreased by regulatory T cells and increased in response to pathogen-derived signals. In this study, we demonstrate that IL-21 can trigger potent and sustained CD86 upregulation through a STAT3 and PI3K-dependent mechanism. We show that elevated CD86 expression has functional consequences for the magnitude of CD4 T cell responses both in vitro and in vivo. These data pinpoint CD86 upregulation as an additional mechanism by which IL-21 can elicit immunomodulatory effects.

Original languageEnglish
Pages (from-to)2195-2201
Number of pages7
JournalJournal of Immunology
Issue number5
Early online date21 Feb 2014
Publication statusPublished - 1 Mar 2014


  • CD86 antigens
  • B-lymphocytes
  • interleukins
  • phosphatidylinositol 3-kinases
  • STAT3 transcription factor
  • T-lymphocytes
  • up-regulation


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