title: Active tuberculosis is characterized by an antigen specific and strictly localized expansion of effector T cells at the site of infection.
abstract: Mycobacterium tuberculosis (MTB)-specific cytokine responses in the peripheral blood and at the site of infection may differ significantly within the same individual, but the under-lying T-cell subset changes are largely unknown. Here, we measured effector and memory T-cell markers on CD4⁺ T cells (CD45RO, cysteine chemokine receptor (CCR)7, and CD27) in peripheral blood and at the site of active tuberculosis (TB). Additionally, T cells were stimulated overnight with purified protein derivative (PPD) and early secretory antigenic target (ESAT)-6 to determine which T-cell subset produces MTB-specific interferon (IFN)-γ. A striking decrease in CCR7 and CD27 expression on T cells was noted at the site of active TB. Likewise, IFN-γ expressing, ESAT-6 specific CD4⁺CD45RO⁺CD27⁻ T cells were dramatically increased at the site of infection but were not detectable in peripheral blood. An antigen-specific expansion of differentiated T cells at the site of active TB infection was poorly reflected in peripheral blood. Insight in these changes in MTB-specific effector T cells in different compartments of the body could lead to new approaches for immune-based diagnosis and interventions.
authors: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors: Johannes
authors: J
authors: Nemeth
authors: Rudolf
authors: R
authors: Rumetshofer
authors: Heide-Maria
authors: HM
authors: Winkler
authors: Otto C
authors: OC
authors: Burghuber
authors: Catharina
authors: C
authors: Müller
authors: Stefan
authors: S
authors: Winkler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D054400:Receptors, CCR7 / Q000097:blood / Q000276:immunology*; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D014373:Tuberculin / Q000494:pharmacology; D014376:Tuberculosis / Q000097:blood / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; C515370:CCR7 protein, human; C525005:ESAT-6 antigen, Mycobacterium leprae; D054400:Receptors, CCR7; D014373:Tuberculin; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens