title: Cytotoxic response persists in subjects treated for tuberculosis decades ago.
abstract: BACKGROUND
  Data exploring the potential use of effector molecules produced by cytotoxic T lymphocytes (CTLs) in the immunodiagnostics of tuberculosis (TB) are scarce. The present study focused a) to gain an insight into the discriminatory power of CTLs in patients with acute pulmonary or extra-pulmonary TB, or latent tuberculosis infection (LTBI); and b) to evaluate the influence of various anti-TB therapeutic schemes on the immunological profiles of residual CTLs.
  
  
  METHODS
  Immunological signatures of antigen-specific CTLs were explored in patients with active pulmonary and extra-pulmonary TB, LTBI and in those treated for TB decades ago by using ELISPOT, intracellular flow cytometry and extracellular CD107a detection.
  
  
  RESULTS
  No difference was seen between active TB, LTBI or any of those treated for TB in the ELISPOT analysis of antigen-specific Granzyme B (GrB), Perforin (Prf) and interferon-gamma (IFN-γ) producing lymphocytes, the FACS analysis of the intracellular expression of IFN-γ, or the surface expression of CD107a degranulation factor of both CD8+ and CD4+ antigen-specific T cell subsets. The effector memory (TEM) phenotype proved predominant in the surface marker profiling both in active TB and LTBI. The proportion of the CD107a degranulation factor proved higher in the central memory (TCM) than in the other cell subsets in all the study groups. Interestingly, functionally and phenotypically similar CTLs profiles were observed in active TB, LTBI and in all the three groups treated for TB.
  
  
  CONCLUSIONS
  The phenotypic and functional profiling of CTLs has a limited potential in the immunodiagnostics of active TB. Antigen-specific CTLs persist in patients treated for TB decades ago regardless of the efficacy of implemented and completed anti-TB therapy.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, PL 21, Helsinki 00014, Finland. laura.e.savolainen@helsinki.fi.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Savolainen
authors.forename: Pekka
authors.initials: P
authors.lastname: Koskivirta
authors.forename: Anu
authors.initials: A
authors.lastname: Kantele
authors.forename: Heikki
authors.initials: H
authors.lastname: Valleala
authors.forename: Liana
authors.initials: L
authors.lastname: Pusa
authors.forename: Riitta
authors.initials: R
authors.lastname: Tuompo
authors.forename: Benita
authors.initials: B
authors.lastname: Westerlund-Wikström
authors.forename: Tamara
authors.initials: T
authors.lastname: Tuuminen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003602:Cytotoxicity, Immunologic; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology*
chemical_list: D052118:Lysosomal-Associated Membrane Protein 1; D007371:Interferon-gamma