Mycobacterium avium and purified protein derivative-specific cytotoxicity mediated by CD4+ lymphocytes from healthy HIV-seropositive and-seronegative individuals.
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.
Ravn
P
P
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
Pedersen
B K
BK
D000328:Adult; D001500:BCG Vaccine; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008297:Male; D016555:Matched-Pair Analysis; D015269:Mycobacterium avium Complex / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014373:Tuberculin / Q000276:immunology*; D014611:Vaccination
D001500:BCG Vaccine; D014373:Tuberculin