title: Variation of Mycobacterium tuberculosis antigen-specific IFN-γ and IL-17 responses in healthy tuberculin skin test (TST)-positive human subjects.
abstract: OBJECTIVE
  To determine the variation of IFN-γ and IL-17 responses to M. tuberculosis antigens in healthy TST+ humans.
  
  
  METHODS
  We isolated peripheral blood mononuclear cells from 21 TST+ healthy adults, stimulated them with phytohemagglutinin (PHA), PPD, Ag85B, ESAT-6, and live M. bovis BCG, and assayed IFN-γ and IL-17 secretion by ELISA in supernatants after 24 or 72 hours of incubation respectively.
  
  
  RESULTS
  As in other studies, we found a wide range of IFN-γ responses to M. tuberculosis antigens; the variation significantly exceeded that observed in the same donors to the polyclonal T cell stimulus, phytohemagglutinin (PHA). In addition, we assayed IL-17 secretion in response to the same stimuli, and found less subject-to-subject variation. Analysis of the ratio of IFN-γ to IL-17 secretion on a subject-to-subject basis also revealed a wide range, with the majority of results distributed in a narrow range, and a minority with extreme results all of which were greater than that in the majority of subjects. The data suggest that study of exceptional responses to M. tuberculosis antigens may reveal immunologic correlates with specific outcomes of M. tuberculosis infection.
  
  
  CONCLUSIONS
  Variation of IFNγ and IFN-γ/IL-17 responses to mycobacterial antigens exceeds that of responses to the polyclonal stimulus, PHA, in TST positive healthy humans. This indicates a quantitative spectrum of human immune responses to infection with M. tuberculosis. Since the outcome of human infection with M. tuberculosis varies greatly, systematic study of multiple immune responses to multiple antigens is likely to reveal correlations between selected immune responses and the outcomes of infection.
authors.affiliation: Division of Infectious Diseases, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Xiao
authors.forename: Zhong-Yi
authors.initials: ZY
authors.lastname: Hu
authors.forename: Joel D
authors.initials: JD
authors.lastname: Ernst
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014019:Tissue Donors; D014374:Tuberculin Test; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D000939:Epitopes; C573415:IFNG protein, human; C508717:IL17A protein, human; D020381:Interleukin-17; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma