title: Functions of invariant NK T cells are modulated by TLR ligands and IFN-α.
abstract: Invariant NK T (iNKT) cells perform numerous immunoregulatory functions. In mice, they express a unique and invariant Vα14-Jα18 rearrangement of α chain in their TCR recognizing glycolipid Ags presented by CD1d. This recognition results in the rapid release of both Th1- and Th2-type cytokines, making them early mediators of the immune response. Owing to their rapid activation and genetic rigidity of their TCR, iNKT cells share characteristics with innate lymphocytes. Therefore, we investigated whether iNKT cells could be induced to express TLRs, a class of pathogen recognition receptor. Mouse iNKT cells were stimulated with anti-CD3 monoclonal Ab and IFN-α, resulting in an increase in the transcription of TLRs 3, 5, 7 and 9, and increased surface expression of TLR3. These cells were subsequently stimulated with TLR ligands, resulting in an increase in the production of IFN-γ, IL-4 and TNF-α. Supernatants from these cells also increased macrophage production of IL-6 and prostaglandin E2, and increased their phagocytic activity and CD80 expression. These supernatants also reduced vesicular stomatitis virus-GFP replication in fibroblasts. This study demonstrates the role of IFN-α in iNKT cell activation, as well as the direct modulatory effects of TLR ligands on iNKT cell function, including antiviral activity.
authors.affiliation: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
authors.forename: A Ian
authors.initials: AI
authors.lastname: Villanueva
authors.affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
authors.forename: S M Mansour
authors.initials: SM
authors.lastname: Haeryfar
authors.affiliation: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Mallard
authors.affiliation: Department of Pediatrics and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Raveendra R
authors.initials: RR
authors.lastname: Kulkarni
authors.affiliation: Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada shayan@uoguelph.ca.
authors.forename: Shayan
authors.initials: S
authors.lastname: Sharif
mesh_terms: D000818:Animals; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D016898:Interferon-alpha / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D055611:Natural Killer T-Cells; D018353:Rhabdoviridae Infections / Q000276:immunology*; D051193:Toll-Like Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D018116:Vesiculovirus / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D016898:Interferon-alpha; D008024:Ligands; D051193:Toll-Like Receptors
keywords: CpG; IFN-α; TLR; antiviral; iNKT cell; macrophage