title: LAPCs promote follicular helper T cell differentiation of Ag-primed CD4+ T cells during respiratory virus infection.
abstract: The humoral immune response to most respiratory virus infections plays a prominent role in virus clearance and is essential for resistance to reinfection. T follicular helper (Tfh) cells are believed to support the development both of a potent primary antibody response and of the germinal center response critical for memory B cell development. Using a model of primary murine influenza A virus (IAV) infection, we demonstrate that a novel late activator antigen-presenting cell (LAPC) promotes the Tfh response in the draining lymph nodes (dLNs) of the IAV-infected lungs. LAPCs migrate from the infected lungs to the dLN "late," i.e., 6 d after infection, which is concomitant with Tfh differentiation. LAPC migration is CXCR3-dependent, and LAPC triggering of Tfh cell development requires ICOS-ICOSL-dependent signaling. LAPCs appear to play a pivotal role in driving Tfh differentiation of Ag-primed CD4(+) T cells and antiviral antibody responses.
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Jae-Kwang
authors.initials: JK
authors.lastname: Yoo
authors.forename: Eleanor N
authors.initials: EN
authors.lastname: Fish
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Braciale
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D018858:Germinal Center / Q000276:immunology; D056724:Immunity, Humoral; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000378:metabolism; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology; D011485:Protein Binding; D054367:Receptors, CXCR3 / Q000378:metabolism; D010253:Respirovirus Infections / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000941:Antigens; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D054367:Receptors, CXCR3