title: Higher frequency of T-cell response to M. tuberculosis latency antigen Rv2628 at the site of active tuberculosis disease than in peripheral blood.
abstract: BACKGROUND
  Due to the invasive nature of the procedures involved, most studies of Mycobacterium tuberculosis (Mtb)-specific immunity in humans have focused on the periphery rather than the site of active infection, the lung. Recently, antigens associated with Mtb-latency and -dormancy have been described using peripheral blood (PB) cells; however their response in the lung is unknown. The objective of this report was to evaluate, in patients prospectively enrolled with suspected active tuberculosis (TB), whether the latency antigen Rv2628 induces local-specific immune response in bronchoalveolar lavage (BAL) cells compared to PB cells.
  
  
  METHODS
  Among the 41 subjects enrolled, 20 resulted with active TB. Among the 21 without active disease, 9 were defined as subjects with latent TB-infection (LTBI) [Quantiferon TB Gold In-tube positive]. Cytokine responses to Rv2628 were evaluated by enzyme linked immunospot (ELISPOT) assay and flow cytometric (FACS) analysis. RD1-secreted antigen stimulation was used as control.
  
  
  RESULTS
  There was a significantly higher frequency of Rv2628- and RD1-specific CD4+ T-cells in the BAL of active TB patients than in PB. However the trend of the response to Rv2628 in subjects with LTBI was higher than in active TB in both PB and BAL, although this difference was not significant. In active TB, Rv2628 and RD1 induced a cytokine-response profile mainly consisting of interferon (IFN)-γ-single-positive over double-IFN-γ/interleukin (IL)-2 T-cells in both PB and BAL. Finally, BAL-specific CD4+ T-cells were mostly effector memory (EM), while peripheral T-cell phenotypes were distributed among naïve, central memory and terminally differentiated effector memory T-cells.
  
  
  CONCLUSIONS
  In this observational study, we show that there is a high frequency of specific T-cells for Mtb-latency and RD1-secreted antigens (mostly IFN-γ-single-positive specific T-cells with an EM phenotype) in the BAL of active TB patients. These data may be important for better understanding the pathogenesis of TB in the lung.
authors.affiliation: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases-INMI, IRCCS, Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Chiacchio
authors.forename: Elisa
authors.initials: E
authors.lastname: Petruccioli
authors.forename: Valentina
authors.initials: V
authors.lastname: Vanini
authors.forename: Ornella
authors.initials: O
authors.lastname: Butera
authors.forename: Gilda
authors.initials: G
authors.lastname: Cuzzi
authors.forename: Linda
authors.initials: L
authors.lastname: Petrone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matteucci
authors.forename: Francesco Nicola
authors.initials: FN
authors.lastname: Lauria
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000097:blood* / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007159:Immunologic Tests; D007371:Interferon-gamma / Q000276:immunology*; D055985:Latent Tuberculosis / Q000097:blood* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D007371:Interferon-gamma
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