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

• Published in: Immunology 1998-12, Vol.95 (4), p.585-590
• Main Authors: Wilkinson, R J, Zhu, X, Wilkinson, K A, Lalvani, A, Ivanyi, J, Pasvol, G, Vordermeier, H M
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; AIDS/HIV; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - immunology; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Enzyme-Linked Immunosorbent Assay - methods; Female; Humans; Interferon-gamma - analysis; Interferon-gamma - metabolism; Male; Middle Aged; Molecular Weight; Mycobacterium tuberculosis - immunology; Tuberculosis - immunology; Tuberculosis - transmission; Vaccines, Synthetic - administration & dosage; Vaccinia - immunology; Viral Vaccines - administration & dosage
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1046/j.1365-2567.1998.00648.x

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 38 000 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.