[Basic studies on tuberculosis and tubercle bacilli in U.S.-Japan medical cooperative program tuberculosis panel]

The U.S.-Japan Medical Cooperative Program has been started in 1965 and Tuberculosis Panel is one of the most important field of the programs. In this lecture, the recent advances in the basic studies on tuberculosis researches which were reported in Tuberculosis panel of the program were summarized. The host defence mechanisms against M. tuberculosis infection were the most important subject. The role of Th1-mediated cytokins such as IL-2, IFN gamma and TNF beta in the host-defence mechanism against mycobacterial infection was extensively discussed. Bcg gene of the mice is the example case for the genetic background of host against mycobacterial infection. The virulence factor, however of M. tuberculosis is still unknown. The technique of molecular biology was applied to the diagnosis of tuberculosis. The PCR and RFLP methods are the useful strategies for the rapid diagnosis and analysis of the mode of infection with M. tuberculosis. The development of detection techniques of drug-resistant tubercle bacilli is also urgently required. Another approach by molecular biology to tuberculosis research is the cloning of gene of tuberculin protein and the production recombinant protein of M. tuberculosis. The amino acid sequences of several proteins have been determined and their immunological properties of recombinant proteins were investigated. The immunological functions of lipid fractions of tubercle bacilli such as cord factor (TDM) and lipoarabinomannan (LAM) have been described. Especially the immunomodulating activities and the role of TDM as diagnostic antigen in the tuberculosis patients were described. The adjuvant activity of mycobacterial cell wall was well established and the minimum structural requirement was reported to be N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). The several MDP derivatives were selected as the cytokine inducers. Especially MDP-Lys (L18) was widely used as drug for the increasing the number of white blood cells and platelets in cancer patients. The effectiveness of MDP derivatives on the stimulating of mucosal immunity was also recently reported. The preventing activities of virus infection and cancer metastasis of MDP derivatives were shown in mice models.