The standard
tuberculin skin test has been known as the prototype of delayed type
hypersensitivity testing which is mediated by T cells and macrophages and plays an important role in the pathogenesis of
tuberculosis.
Tuberculosis is indeed a chronic
infectious disease, but variation in the host immune responses to tubercle bacilli results in the various clinical manifestations of the disease ranging from an immunologically hyperreactive state observed in pleural fluid lymphocytes in
tuberculous pleurisy to an almost totally unresponsive state observed in those severely ill with refractory
tuberculosis. In
tuberculous pleurisy, T cells in pleural fluid respond remarkably in vitro to
PPD tuberculin whereas T cells in peripheral blood responded poorly to
PPD stimulation. Compartmentalization of
PPD-reactive T cells in the pleural fluid and immunosuppression by T cells and/or macrophages in the peripheral blood were responsible for this immunological difference observed between the lymphocytes in pleural fluid and those in peripheral blood of
tuberculous pleurisy. In advanced,
drug-resistant tuberculosis as well as in nontuberculous mycobacterial
infection, the proliferative responses of T cells in vitro to
PPD stimulation were impaired. This depressed T cell response was due to depressed
interleukin-2 (IL-2) production and not due to depressed
IL-2 responsiveness. Therefore, the addition of exogenous
IL-2, returned the depressed
PPD-induced lymphocyte proliferation in vitro in these patients to the level of the response observed in lymphocytes from patients with newly-diagnosed
tuberculosis. Our results suggest that recombinant
IL-2 offers a novel approach to the
therapy of advanced,
drug-resistant tuberculosis and nontuberculous mycobacterial
infection. Preliminary clinical trials of
immunotherapy with recombinant
IL-2 reveals the effectiveness of this
therapy and encourages us to extend the trial to a larger scale. Tubercle bacilli have various
biological activities. Research on
tuberculosis and tubercle bacilli have contributed much to the progress of biochemistry, pathology and immunology. Mycobacterium is a fascinating organism, which now presents another big appeal to those studying immunology: Study of immunological interaction between gamma delta T cells and the highly conserved
protein in mycobacteria, HSP,
heat shock protein will contribute to the elucidation of the mechanism of immunological surveillance and the mechanism of
autoimmune diseases. In addition, it will also contribute to the development of a new mycobacterial
vaccine which will give direct, protective immunity against
tuberculosis.