The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance
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.
|Authors||Meli, A. P.; Fontes, G.; Avery, D. T.; Leddon, S. A.; Tam, M.; Elliot, M.; Ballesteros-Tato, A.; Miller, J.; Stevenson, M. M.; Fowell, D. J.; Tangye, S. G.; King, I. L.;|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/27760339|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/13424|