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Peripheral blood mononuclear cells from patients with advanced disseminated tuberculosis (Dis-TB) do not respond to purified protein derivative (PPD) measured as cell proliferation, lymphokine production and interleukin (IL)-2 receptor (Tac antigen) expression. Limiting dilution analysis revealed "multi-hit" curves and low frequencies of PPD-reactive T cells in cultures of Dis-TB, and "single-hit" curves and high frequencies of PPD-reactive T cells in cultures of patients with localized form of pulmonary tuberculosis. Moreover, a strict relationship between Tac antigen expression and ability of exogenous IL-2 to enhance bulk culture cell proliferation was observed in Dis-TB patients.

Tuberculosis is still one of the major health problems in almost all over the world. Thus, new directions in basic and applied research on tuberculosis are under investigation. In this review we have provided recent data obtained in our laboratories on three main aspects of the immunology of tuberculosis, namely: i. the role of B lymphocytes in the processing and presentation of Mycobacterium tuberculosis antigens to T cells; ii. the activation and characterization of mycobacterial-specific T cell clones; iii. the T cell regulation of the immune response to M. tuberculosis. The analysis of the antigenic determinants of M. tuberculosis relevant in the antimycobacterial immunity is the major goal of the WHO programme on the immunology of tuberculosis. In fact, the attempt to develop a second generation vaccine against this microorganism is now possible by analyzing recombinant genomic DNA libraries of M. tuberculosis with monoclonal antibodies and T cell clones. In the near future, the identification of epitopes recognized by mycobacterial-specific T cells with helper, cytotoxic and suppressor functions will allow the preparation of recombinant and synthetic vaccines effective in the control of this disease.

We have analyzed the presentation of mycobacterial antigens by Epstein-Barr virus-transformed human B (EBV-B) cells to mycobacteria-specific T-cell clones and lines, and to purified resting T cells. EBV-B cells were able to process and present not only soluble forms of antigen, such as PPD and the expressate preparation of M. tuberculosis strain H37Rv, but also particulate forms of antigen, such as whole mycobacterial H37Rv or M. bovis organisms. Electron microscopy studies demonstrated the capacity of EBV-B cells to phagocytose mycobacterial cells in 18 hr and pulsing experiments confirmed that an 18-hr of incubation is required for an efficient processing and presentation of mycobacterial determinants to T cells. The processing of whole-H37Rv particulate antigen by EBV-B cells was inhibited by the lysosomotrophic compound chloroquine and by high doses of irradiation. Finally, the analysis of the presentation of soluble and particulate mycobacterial antigens by PPD-positive and PPD-negative EBV-B cell clones has shown a preferential presentation of both forms of antigen by PPD-positive EBV-B clones.