title: The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance.
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.
authors.affiliation: Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Meli
authors.affiliation: Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Fontés
authors.affiliation: The Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
authors.forename: Danielle T
authors.initials: DT
authors.lastname: Avery
authors.affiliation: Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Leddon
authors.affiliation: Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Mifong
authors.initials: M
authors.lastname: Tam
authors.affiliation: Sydney Head and Neck Cancer Institute, Camperdown, NSW 2050, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Elliot
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Ballesteros-Tato
authors.affiliation: Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Miller
authors.affiliation: Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Stevenson
authors.affiliation: Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Fowell
authors.affiliation: The Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Tangye
authors.affiliation: Department of Microbiology and Immunology, Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec H3A 2B4, Canada. Electronic address: irah.king@mcgill.ca.
authors.forename: Irah L
authors.initials: IL
authors.lastname: King
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D051560:Proto-Oncogene Proteins c-bcl-6