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

Immunity. 2016 Oct 18;45(4):831-846. doi: 10.1016/j.immuni.2016.09.018.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Germinal Center / immunology
  • Humans
  • Immunity, Humoral / immunology
  • Lymphocyte Activation / immunology*
  • Lymphocyte Function-Associated Antigen-1 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-bcl-6 / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Lymphocyte Function-Associated Antigen-1
  • Proto-Oncogene Proteins c-bcl-6