title: Specific lytic activity against mycobacterial antigens is inversely correlated with the severity of tuberculosis.
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.
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Hematológicas (IIHema), Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: S S
authors.initials: SS
authors.lastname: De La Barrera
authors.forename: M
authors.initials: M
authors.lastname: Finiasz
authors.forename: A
authors.initials: A
authors.lastname: Frias
authors.forename: M
authors.initials: M
authors.lastname: Alemán
authors.forename: P
authors.initials: P
authors.lastname: Barrionuevo
authors.forename: S
authors.initials: S
authors.lastname: Fink
authors.forename: M C
authors.initials: MC
authors.lastname: Franco
authors.forename: E
authors.initials: E
authors.lastname: Abbate
authors.forename: M
authors.initials: M
authors.lastname: del C  Sasiain
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008285:Major Histocompatibility Complex; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D017252:CD3 Complex; D018950:Lipopolysaccharide Receptors; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014373:Tuberculin