Although natural killer (NK) cells, which lyse certain tumors in vitro, have been shown to provide early defense mechanism against cancer growth and viral infection, possible role in the host defense against pulmonary tuberculosis remains undefined. A series of my studies have recently provided several evidence supporting the involvement of NK cells in the immunopathology of pulmonary tuberculosis.
NK cell activity in patients with active pulmonary tuberculosis was significantly aug mented compared with that in age-, sex- matched healthy controls, which suggests NK cells are activated in vivo in pulmonary tuberculosis. Lung NK cells from BCG-infected mice also are shown to be activated. Asialo GM 1 was demonstrated to be a novel sur face marker of mice NK cells, which inhibited activation of NK cells by interferon.
Chronic intractable tuberculosis was classified with a combination of NK cell activity and delayed-type hypersensitivity reaction to 2, 4-dinitrochrolbenzene. Subgroup defined with high NK cell activity and normal delayed-type hypersensitivity was characterized with moderate radiographical lesions and stable clinical course, suggesting the immunespectrum classification was associated with clinical manifestations.
Malnutrition has been suggested to be a risk factor associated with the development and reactivation of pulmonary tuberculosis. NK cell activity was significantly correlated with visceral proteins. IL-2 producing capability was significantly decreased in patients with serum albumin less than 3.5g/dl.
More recently, I established an in vitro system evaluating quantitative capability for intracellular killing by human monocytes, in which monocyte phagocytize Mycobacterium tuberculosis and subsequently inhibit intracellular replication of the organisms by adding some cytokines or cells. Purified NK cells by using discontinuous gradient centrifugation and magnetic separation technique were added to M. tuberculosis-infected monocytes monolayer. Purified NK cells inhibit intracellular replication within monocytes in dose re sponse manner.
In conclusion these findings suggest that (1) NK cells are activated in pulmonary tu berculosis and that (2) NK cells are related with nutritional status and that (3) the immune spectrum defined by NK cell and delayed-type hypersensitivity are related with clinical manifestations and that (4) NK cells may be involved with an early defense mechanism in terms of activation of intracellular killing by human monocyte/macrophage system.
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