title: 38 000 MW antigen-specific major histocompatibility complex class I restricted interferon-gamma-secreting CD8+ T cells in healthy contacts of tuberculosis.
abstract: CD8+ T lymphocytes are required to protect mice against Mycobacterium tuberculosis, although in early infection the mechanism appears not to be via perforin or granzyme-mediated lysis of the infected target, and may be via interferon-gamma (IFN-gamma) production. We therefore investigated whether CD8+ T cells specific for the immunoprotective 38 000 MW antigen of M. tuberculosis could be detected in infected humans. Using a recombinant vaccinia virus expressing the 38 000 MW antigen of M. tuberculosis (rV38) and a control vaccinia virus (rVras) we demonstrated that both viruses stimulated IFN-gamma production from freshly isolated peripheral blood mononuclear cells (PBMC) in a 36-hr enzyme-linked immunospot assay. Cell depletion and antibody blockade established that the bulk of the 38 000 MW antigen-specific IFN-gamma response was mediated by CD8+, major histocompatibility complex class I-restricted T cells, whereas the anti-vaccinia virus response was predominantly mediated by CD4+ T cells. In further evaluations PBMC from all seven healthy tuberculosis-exposed contacts had a 38 000 MW antigen-specific IFN-gamma response, whereas seven patients with untreated sputum-positive pulmonary tuberculosis had very low levels of 38 000 antigen-specific IFN-gamma-producing cells. These preliminary observations demonstrate the utility of recombinant vaccinia viruses in restimulating freshly isolated CD4+ and CD8+ T cells. The bias towards a higher frequency of IFN-gamma-producing CD8+ T cells in contacts rather than patients may indicate a protective role for CD8+ cells in human tuberculosis.
authors.affiliation: Tuberculosis and Related Infections Unit, Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: K A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: A
authors.initials: A
authors.lastname: Lalvani
authors.forename: J
authors.initials: J
authors.lastname: Ivanyi
authors.forename: G
authors.initials: G
authors.lastname: Pasvol
authors.forename: H M
authors.initials: HM
authors.lastname: Vordermeier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000635:transmission; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014615:Vaccinia / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage
chemical_list: D000942:Antigens, Bacterial; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D007371:Interferon-gamma