title: In vivo depletion of CD11c+ cells delays the CD4+ T cell response to Mycobacterium tuberculosis and exacerbates the outcome of infection.
abstract: Although dendritic cells (DC) are potent APC that prime T cells against many pathogens, there is no direct evidence that DC are required for immunity to Mycobacterium tuberculosis (Mtb) infection. The requirement for DC to prime the CD4+ T cell response following Mtb infection was investigated using pCD11c-diptheria toxin receptor/GFP transgenic mice, in which DC can be transiently ablated in vivo. We show a critical role for DC in initiation of the CD4+ T cell response to the mycobacterial Ag early secretory Ag of tuberculosis 6. The delay in initiating the Ag-specific T cell response led to impaired control of Mtb replication. Interestingly, DC were not required for the secondary CD4+ T cell response following Mtb infection in peptide-vaccinated mice. Thus, this study shows that DC are essential for the initiation of the adaptive T cell response to the human pathogen Mtb.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.forename: Joshua
authors.initials: J
authors.lastname: Woodworth
authors.forename: Markus
authors.initials: M
authors.lastname: Sköld
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Behar
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins; D039521:CD11c Antigen / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology; D014611:Vaccination
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D039521:CD11c Antigen; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma