38 000 MW antigen-specific major histocompatibility complex class I restricted interferon-γ-secreting CD8+ T cells in healthy contacts of tuberculosis

R. J. Wilkinson*, X. Zhu, K. A. Wilkinson, A. Lalvani, J. Ivanyi, G. Pasvol, H. M. Vordermeier

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (SciVal)

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-γ (IFN-γ) 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 38000 MW antigen of M. tuberculosis (rV38) and a control vaccinia virus (rVras) we demonstrated that both viruses stimulated IFN-γ 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-γ 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-γ response, whereas seven patients with untreated sputum-positive pulmonary tuberculosis had very low levels of 38 000 antigen-specific IFN-γ-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-γ-producing CD8+ T cells in contacts rather than patients may indicate a protective role for CD8+ cells in human tuberculosis.

Original languageEnglish
Pages (from-to)585-590
Number of pages6
JournalImmunology
Volume95
Issue number4
DOIs
Publication statusPublished - 21 Dec 1998

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Bacterial/administration & dosage
  • CD8-Positive T-Lymphocytes/immunology
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay/methods
  • Female
  • Humans
  • Interferon-gamma/analysis
  • Male
  • Middle Aged
  • Molecular Weight
  • Mycobacterium tuberculosis/immunology
  • Tuberculosis/immunology
  • Vaccines, Synthetic/administration & dosage
  • Vaccinia/immunology
  • Viral Vaccines/administration & dosage

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