ABSTRACT
The ability of peripheral blood mononuclear cells (PBMC) from patients with active tuberculosis to display cytotoxic responses against autologous Mycobacterium tuberculosis (Mtb)-pulsed macrophages was evaluated. Non-MHC restricted cell-dependent lytic activity was observed in ex vivo effector cells from tuberculosis patients and was mediated mainly by CD3(+)gammadelta TCR(+) T (gammadelta T) cells bearing CD56 and/or CD16 molecules. MHC-restricted and non-MHC restricted cytotoxic T cells (CTL) were differentially expanded upon stimulation with Mtb in tuberculosis patients and normal controls (N). Class-I restricted CD8(+) CTL and class-II restricted CD4(+) CTL were generated in PPD(+)N and to a lesser extent in PPD(-)N. Mtb-stimulated effector cells from tuberculosis patients became progressively non-MHC restricted CD4(-)CD8(-)gammadelta T cells, while lytic activity of CD4(+) and CD8(+)CTL decreased gradually as the disease became more severe. On the other hand, target cells were lysed by ex vivo cells from tuberculosis patients through the Fas-FasL and perforin pathways. Mtb-induced CD4(+) CTL from tuberculosis patients and N controls preferentially employed the Fas-FasL mechanism. Mtb-induced CD8(+) CTL effector cells from patients used the perforin-based mechanism while cells from N controls also used the Fas-FasL pathway. While Mtb-induced gammadelta CTL from patients and PPD(-)N employed the latter mechanism cells from PPD(+)N individuals also used the perforin pathway. It can be concluded that shifts in the CTL response and the cytolytic mechanisms take place as the pulmonary involvement becomes more severe.
Subject(s)
Antigens, Bacterial/immunology , Cytotoxicity, Immunologic , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/immunology , Adult , Aged , CD3 Complex/analysis , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cells, Cultured , Female , Humans , Lipopolysaccharide Receptors/analysis , Lymphocyte Activation/immunology , Macrophages/immunology , Major Histocompatibility Complex , Male , Middle Aged , Receptors, Antigen, T-Cell, gamma-delta/analysis , T-Lymphocytes, Cytotoxic/immunology , Tuberculin/immunologyABSTRACT
The immunological competence of eleven patients with undetermined leprosy was compared with that of ten normal volunteers of the same age and sex distribution; these controls have not had previous contact with leprosy. The following parameters were studied in peripheral blood cells: 1) percentage of lymphocyte bearing surface immunoglobulins, as revealed by immunofluorescence; 2) percentage of lymphocyte bearing complement receptors, as studied by antibody and complement coated erithrocyte rosetting; 3) percentage of T cells, as revealed by spontaneous sheep erithrocyte rosettes; 4) blastogenic and mytogenic response of cultured lymphocytes to PHA and 5) cell migration inhibition test using lepromine (80 x 10(6) bacilli/ml) as antigen. Skin reactions to lepromine were also assayed. In the six lepromine-positive patients with undetermined leprosy, no major immunological alterations could be detected. On the contrary, the five lepromine-negative patients showed important alterations which could well be considered as precursors of lepromatous leprosy.
Subject(s)
Immunity , Leprosy/immunology , Adult , Female , Humans , MaleABSTRACT
The immunological competence of eleven patients with undetermined leprosy was compared with that of ten normal volunteers of the same age and sex distribution; these controls have not had previous contact with leprosy. The following parameters were studied in peripheral blood cells: 1) percentage of lymphocyte bearing surface immunoglobulins, as revealed by immunofluorescence; 2) percentage of lymphocyte bearing complement receptors, as studied by antibody and complement coated erithrocyte rosetting; 3) percentage of T cells, as revealed by spontaneous sheep erithrocyte rosettes; 4) blastogenic and mytogenic response of cultured lymphocytes to PHA and 5) cell migration inhibition test using lepromine (80 x 10(6) bacilli/ml) as antigen. Skin reactions to lepromine were also assayed. In the six lepromine-positive patients with undetermined leprosy, no major immunological alterations could be detected. On the contrary, the five lepromine-negative patients showed important alterations which could well be considered as precursors of lepromatous leprosy.
ABSTRACT
The immunological competence of eleven patients with undetermined leprosy was compared with that of ten normal volunteers of the same age and sex distribution; these controls have not had previous contact with leprosy. The following parameters were studied in peripheral blood cells: 1) percentage of lymphocyte bearing surface immunoglobulins, as revealed by immunofluorescence; 2) percentage of lymphocyte bearing complement receptors, as studied by antibody and complement coated erithrocyte rosetting; 3) percentage of T cells, as revealed by spontaneous sheep erithrocyte rosettes; 4) blastogenic and mytogenic response of cultured lymphocytes to PHA and 5) cell migration inhibition test using lepromine (80 x 10(6) bacilli/ml) as antigen. Skin reactions to lepromine were also assayed. In the six lepromine-positive patients with undetermined leprosy, no major immunological alterations could be detected. On the contrary, the five lepromine-negative patients showed important alterations which could well be considered as precursors of lepromatous leprosy.
