title: Type-1 polarised dendritic cells are a potent immunogen againstMycobacterium tuberculosis.
abstract: Application of immunotherapy using dendritic cells (DCs) is considered an effective treatment strategy against persistent Mycobacterium tuberculosis infection. With the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (TB), we tested the ability of ex vivo-generated DCs to induce an effective TB antigen-specific type-1 immune response.
  
  
  
  Monocyte-derived DCs from TB patients were induced to mature using a 'standard' cytokine cocktail (interleukin [IL] 1β, tumour necrosis factor alpha [TNF-α], IL-6 and prostaglandin E2) or a type 1-polarised DC (DC1) cocktail (IL-1β, TNF-α, interferon [IFN] α, IFN-γ and polyinosinic:polycytidylic acid), and were loaded with the established TB antigen 6-kDa early secretory antigenic target protein (ESAT-6).
  
  
  
  Although DC1s from TB patients expressed the same levels of multiple co-stimulatory molecules (CD83, CD86, CD80 and CD40) as the standard DCs (sDCs), DC1s secreted substantially higher levels of IL-12p70. Furthermore, when DCs pulsed with or without ESAT-6 were cultured with lymphocytes from the same patients, DC1s induced much higher numbers of ESAT-6-specific IFN-γ-producing T-cells than sDCs, as manifested by their superior induction of natural killer cell activation and antigen-independent suppression of regulatory T-cells.
  
  
  
  TB antigen-loaded DC1s are potent inducers of antigen-specific T-cells, which could be used to develop improved immunotherapies of TB.
authors.affiliation: Second Division, Department of Internal Medicine.
authors.forename: Y
authors.initials: Y
authors.lastname: Satake
authors.affiliation: Second Division, Department of Internal Medicine.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Second Division, Department of Internal Medicine.
authors.forename: M
authors.initials: M
authors.lastname: Kono
authors.affiliation: Second Division, Department of Internal Medicine.
authors.forename: H
authors.initials: H
authors.lastname: Hozumi
authors.affiliation: Department of Health Science.
authors.forename: T
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Infectious Disease, Department of Health Science.
authors.forename: K
authors.initials: K
authors.lastname: Tsujimura
authors.affiliation: Second Division, Department of Internal Medicine.
authors.forename: N
authors.initials: N
authors.lastname: Enomoto
authors.affiliation: Second Division, Department of Internal Medicine.
authors.forename: T
authors.initials: T
authors.lastname: Fujisawa
authors.affiliation: Second Division, Department of Internal Medicine, Department of Clinical Pharmacology and Therapeutics.
authors.forename: N
authors.initials: N
authors.lastname: Inui
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu.
authors.forename: T
authors.initials: T
authors.lastname: Fujiyama
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu.
authors.forename: Y
authors.initials: Y
authors.lastname: Tokura
authors.affiliation: Department of Respiratory Medicine, Seirei Mikatahara General Hospital, Hamamatsu.
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Respiratory Medicine, Seirei Mikatahara General Hospital, Hamamatsu.
authors.forename: K
authors.initials: K
authors.lastname: Yokomura
authors.affiliation: Department of Health Science, Second Division, Department of Internal Medicine.
authors.forename: M
authors.initials: M
authors.lastname: Shirai
authors.affiliation: Second Division, Department of Internal Medicine, Second Division, Department of Internal Medicine.
authors.forename: H
authors.initials: H
authors.lastname: Hayakawa
authors.affiliation: Second Division, Department of Internal Medicine.
authors.forename: T
authors.initials: T
authors.lastname: Suda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D055611:Natural Killer T-Cells / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000628:therapy*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D018664:Interleukin-12