Defective Interleukin 2 Production in Tuberculosis

Some patients with active tuberculosis lack a delayed skin test reaction to PPD (1-4). The basis for this immunologic hyporesponsiveness has been investigated using in vitro systems. Tuberculin-induced blastogenic responses of lymphocytes are decreased in such patients compared with healthy tuberculin reactors (5, 6). This is not simply due to a dearth of responsive cells in the circulation. Rather, monocytes act as antigen-specific suppressor cells in patients with pulmonary tuberculosis (5) and tuberculous pleurisy (8). FcTR + lymphocytes, i.e., cells bearing receptors for the Fc portion of IgG, also suppress PPD-induced blastogenesis in tuberculous patients (9). T cell proliferation is critically dependent on the lymphokine, IL-2 (10, 1 1). This hormone is a prerequisite for clonal expansion of antigen-specific T cells (12) and activation of the effector limb of cell-mediated immune responses (13, 14). IL-2-dependent cytotoxicity may be important for containment of facultative intracellular parasites such as Mycobacterium leprae (15) and Mycobacterium tuberculosis. We investigated IL-2 homeostasis in patients with active, newly diagnosed pulmonary tuberculosis. Depressed PPD-induced blastogenesis in these patients was associated with abnormalities in IL-2 production and IL-2-R generation restricted to the response to tuberculin PPD. In 10 of 22 patients, IL-2 generation was depressed and unaffected by adherent cell depletion; these patients showed more extensive disease by radiographic criteria. Dysregulation of production and response to the pivotal cytokine IL-2 thus may be critical factors in the defective cellular immune response in tuberculosis.