The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance

Academic Article

Abstract

  • T follicular helper (Tfh) cells are a CD4 T cell subset critical for long-lived humoral immunity. We hypothesized that integrins play a decisive role in Tfh cell biology. Here we show that Tfh cells expressed a highly active form of leukocyte function-associated antigen-1 (LFA-1) that was required for their survival within the germinal center niche. In addition, LFA-1 promoted expression of Bcl-6, a transcriptional repressor critical for Tfh cell differentiation, and inhibition of LFA-1 abolished Tfh cell generation and prevented protective humoral immunity to intestinal helminth infection. Furthermore, we demonstrated that expression of Talin-1, an adaptor protein that regulates LFA-1 affinity, dictated Tfh versus Th2 effector cell differentiation. Collectively, our results define unique functions for LFA-1 in the Tfh cell effector program and suggest that integrin activity is important in lineage decision-making events in the adaptive immune system. +
  • Published In

  • Immunity  Journal
  • Digital Object Identifier (doi)

    Author List

  • Meli AP; Fontés G; Avery DT; Leddon SA; Tam M; Elliot M; Ballesteros-Tato A; Miller J; Stevenson MM; Fowell DJ
  • Start Page

  • 831
  • End Page

  • 846
  • Volume

  • 45
  • Issue

  • 4