title: IFNγ/TNFα specific-cells and effector memory phenotype associate with active tuberculosis.
abstract: OBJECTIVE
  Controversial results were reported on the role of polyfunctional T-cells in tuberculosis (TB). Our aim was to simultaneously characterize the Mycobacterium tuberculosis (Mtb)-specific immune response as cytokine production and memory phenotype by flow cytometry after in vitro stimulation with region of difference 1 ("RD1") recombinant proteins (ESAT-6 and CFP-10) in patients at different TB stage in a low TB endemic country. To assess the specificity of these findings, we evaluated the response to cytomegalovirus (CMV), an unrelated antigen.
  
  
  METHODS
  We enrolled subjects with active TB, cured TB, latent TB infection (LTBI). Cytokine and phenotype profiles of T-cells from whole blood stimulated with "RD1" proteins and CMV were characterized by multi-parametric flow cytometry.
  
  
  RESULTS
  Bifunctional IFNγ(+) TNFα(+) CD4(+) T-cells and effector memory phenotype significantly associated with active TB compared to the LTBI group (p = 0.008, at least p ≤ 0.009 respectively) whereas "RD1"-T-cell response in cured TB and LTBI was characterized by a central memory phenotype (at least p ≤ 0.013 and p ≤ 0.004 respectively vs active TB). In contrast, response to CMV antigen was not associated with a TB-specific status.
  
  
  CONCLUSIONS
  We identified qualitative associations between Mtb-specific T-cell and TB status in terms of functional capacity and memory status. These immune correlates may be helpful to trace natural history of TB.
authors: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Via Portuense 292, 00149 Rome, Italy.
authors: Elisa
authors: E
authors: Petruccioli
authors: Linda
authors: L
authors: Petrone
authors: Valentina
authors: V
authors: Vanini
authors: Alessandro
authors: A
authors: Sampaolesi
authors: Gina
authors: G
authors: Gualano
authors: Enrico
authors: E
authors: Girardi
authors: Fabrizio
authors: F
authors: Palmieri
authors: Delia
authors: D
authors: Goletti
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D000956:Antigens, Viral; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma