Mycobacterium avium and purified protein derivative-specific cytotoxicity mediated by CD4+ lymphocytes from healthy HIV-seropositive and-seronegative individuals

J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Aug 15;12(5):433-41. doi: 10.1097/00042560-199608150-00001.

Abstract

HIV is the greatest single risk factor for the development of tuberculosis. Diseases caused by M. tuberculosis and mycobacteria are the most common opportunistic infections in HIV-infected persons, which may stem from a functional defect of the CD4+ T-cell-mediated killing of macrophages harboring mycobacteria. Our objective was to investigate the M.tuberculosis-and M. avium-specific cytotoxic capacity of T cells from healthy, bacille Calmette-Guérin-vaccinated, HIV-seropositive individuals. Blood mononuclear cells were obtained from 10 healthy HIV-seropositive and 10 healthy seronegative persons with no history of previous or active mycobacterial infection. Antigen-specific killing of macrophages presenting mycobacterial antigens (purified protein derivative or M. avium culture filtrate) was conducted. The phenotype of the killer cells was determined by a fluorescence-activated cell sorter after antigen stimulation and by using purified CD4+ and CD8+ cell subsets. Substantial, but reduced antigen-specific cytotoxicity was observed in patients with asymptomatic HIV infection. The immunological dysfunction leading to reduced cytotoxic activity in healthy HIV-seropositive subjects could not be explained by a defect in the cytotoxic capacity of the individual CD4+ lymphocyte after antigen stimulation, and it could not be explained by a reduction in the total number of CD4+ cells before antigen stimulation. The antigen-specific cytotoxic activity was, however, closely related to the ability of the CD4+ T cells to respond to mycobacterial antigens. The immunological dysfunction leading to reduced mycobacterial-specific cytotoxic activity in healthy HIV-seropositive subjects is caused either by a reduction in the number of antigen-responsive CD4+ T cells (memory) or by an impairment of their ability to respond to antigenic stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • BCG Vaccine
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytotoxicity, Immunologic*
  • Female
  • HIV Seronegativity / immunology
  • HIV Seropositivity / immunology*
  • HIV-1 / immunology
  • Humans
  • Immunologic Memory / immunology
  • Lymphocyte Activation
  • Macrophages / immunology
  • Male
  • Matched-Pair Analysis
  • Mycobacterium avium Complex / immunology*
  • Mycobacterium tuberculosis / immunology
  • T-Lymphocyte Subsets / immunology
  • Tuberculin / immunology*
  • Vaccination

Substances

  • BCG Vaccine
  • Tuberculin