Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis

Abstract

SUMMARYThe cytolytic capacity of mycobacterial antigen-stimulated peripheral blood mononuclear cells, from healthy Mantoux-positive volunteers and from paiients with tuberculosis was investigated. Polyclonal T cell lines induced by 7 days of stimulation in vitro with PPD or a sonicate of Mycobacterium tubercutosis lysed both autologous macrophages and Epstein-Barr virus (EBV) transformed B cell lines which had been pulsed with mycobacterial antigens, to a greater extent than unpulsed target cells or target cells pulsed with an irrelevant antigen (strcptokinasc, streptodornase). The killing of mycobacterial antigen-pulsed macrophages and EBV-transformed B cell line targets was inhibited by monoclonal antibodies to MHC class II antigens but not by antibodies directed against MHC class I antigens. PPD-pulsed EBV-transformed lymphoblasloid cell lines (LCL) competitively inhibited the killing of mycobacterial antigen-pulsed macrophages, whereas natural killer (NK) sensitive K562 cells (with or without antigen pulsing) did not inhibit mycobacterial antigen-dependent cytolysis of macrophages. Patients with tuberculosis showed a spectrum of mycobacterial antigen-induced cytolytic capacity. Those with extensive tissue necrosis (e.g. cavitatory pulmonary tuberculosis or easeous. extrathoracic tuberculosis) had high levels while patients with disseminated (miliary) tuberculosis or disease refractory to treatment showed little evidence of mycobacterial antigen induced cytotoxicity. The ability of mycobacteriai antigenstimulated lymphoblasls to kill specific antigen-pulsed autologous macrophages was not significantly different between healthy donors and patients with tuberculosis. However, the 'mycobacterial antigen-specific" component of this cytolysis was significantly deficient iP<0-0\) in patients. We conclude that mycobacterial antigen-specific cytotoxic T cell responses may play a significant part in the immune response to mycobacterial infection.

Lack of cytotoxic activity against Mycobacterium leprae 65-kD heat shock protein (hsp) in multibacillary leprosy patients

“…1). The development of specific cytotoxicity was directly related to proliferation with all three hsp tested (Fig 2), as has been previously shown by other authors [27,30]. There was no cross-reactivity between the recombinant proteins employed (Table 2), in accordance with the literature [16].…”

“…tuberculosis, and Myco. bovis BCG are potent inducers of antigen-specific HLA-restricted cytotoxic T cells that lyse human macrophages [16,26,30]. In this study we analysed the cytotoxic activity induced by Myco.…”

Reduced NK activity correlates with active disease in HIV- patients with multidrug-resistant pulmonary tuberculosis

“…Recent reports have emphasized the importance of antigenspecific cytotoxicity. mediated by CD4' lymphocytes, in TB [7,8]. In addition, ihere is experimental evidence that natural killer (NK) cells have a significant function in overcoming mycobacterial infection [9,10].…”

Lysis of human macrophages by cytolytic CD4+ T cells fails to affect survival of intracellularMycobacterium bovis-bacille Calmette-Guérin (BCG)

“…Consequently other mechanisms of protection need to be investigated and their antimycobacterial efFects examined. Class Il-restricted T cells have been shown to have cytolytic activity in vitro against mycobacterial-infected cells [4,5]. The relevance of class Il-restricted cytolytic T lymphocytes (CTL) in tuberculosis infections, however, remains controversial, with both protective and pathogenic roles being cited in the literature [6][7][8].…”