title: Human innate Mycobacterium tuberculosis-reactive alphabetaTCR+ thymocytes.
abstract: The control of Mycobacterium tuberculosis (Mtb) infection is heavily dependent on the adaptive Th1 cellular immune response. Paradoxically, optimal priming of the Th1 response requires activation of priming dendritic cells with Th1 cytokine IFN-gamma. At present, the innate cellular mechanisms required for the generation of an optimal Th1 T cell response remain poorly characterized. We hypothesized that innate Mtb-reactive T cells provide an early source of IFN-gamma to fully activate Mtb-exposed dendritic cells. Here, we report the identification of a novel population of Mtb-reactive CD4(-) alphabetaTCR(+) innate thymocytes. These cells are present at high frequencies, respond to Mtb-infected cells by producing IFN-gamma directly ex vivo, and display characteristics of effector memory T cells. This novel innate population of Mtb-reactive T cells will drive further investigation into the role of these cells in the containment of Mtb following infectious exposure. Furthermore, this is the first demonstration of a human innate pathogen-specific alphabetaTCR(+) T cell and is likely to inspire further investigation into innate T cells recognizing other important human pathogens.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Portland VA Medical Center, Oregon Health and Science University, Portland, Oregon, United States of America. goldm@ohsu.edu
authors.forename: Marielle C
authors.initials: MC
authors.lastname: Gold
authors.forename: Heather D
authors.initials: HD
authors.lastname: Ehlinger
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Cook
authors.forename: Susan K
authors.initials: SK
authors.lastname: Smyk-Pearson
authors.forename: Paul T
authors.initials: PT
authors.lastname: Wille
authors.forename: Ross M
authors.initials: RM
authors.lastname: Ungerleider
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lewinsohn
authors.forename: David M
authors.initials: DM
authors.lastname: Lewinsohn
mesh_terms: D002452:Cell Count; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007231:Infant, Newborn; D007370:Interferon Type I / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D016693:Receptors, Antigen, T-Cell, alpha-beta