Defective interleukin 2 production and responsiveness in human pulmonary tuberculosis.

Abstract

Patients with newly diagnosed, pulmonary tuberculosis had a tuberculin-specific defect in IL-2 production. Mean PPD-induced IL-2 activity was 81.2% lower in patients as compared with healthy tuberculin reactors. PPD-induced expression of T cell IL-2 receptors was 5.9 times less in peripheral blood mononuclear cells of patients with tuberculosis as compared with healthy tuberculin reactors. Furthermore, purified IL-2 failed to correct PPD-induced blastogenesis in patients. Suppression by adherent cells was operative in one group of patients; adherent cell depletion increased their T cell production of IL-2 7.2-fold. A second group of patients with low IL-2 production did not have suppressor adherent cells and were clinically distinct, with more extensive disease on chest x ray. The basis for low IL-2 production in such individuals is unknown. Disordered regulation of IL-2 metabolism may be a key feature in the depressed cellular immune response of tuberculosis.

Expression of functional interleukin 2 receptors by peripheral blood monocytes from patients with active pulmonary tuberculosis.

“…Such cells display increased stimulated release of IL 1 (1), augmented adherence to plastic (2), enhanced hexose monophosphate shunt activity (3), altered surface expression of HLA DR antigens (4), and increased killing of some but not all targets (5). Circulating monocytes from patients with TB also selectively depress lymphocyte responses to the mycobacterial antigen, tuberculin purified protein derivative (PPD) (6,7); this activity may contribute to depression of delayed-type hypersensitivity (DTH), as assessed by tuberculin skin tests in such patients. The expression of cell-mediated immune response requires the interaction of IL 2 with its receptor (IL 2R) on the surface of antigen-responsive T cells (8).…”

IL-4 Influences Apoptosis of Mycobacterium-Reactive Lymphocytes in the Presence of TNF-α

“…Infection with Trypanosoma cruzi (1), Toxoplasma gondii (2), and Schistosoma mansoni (3) all result in down-regulation of cell-mediated immunity associated with CD4 ϩ -T cell apoptosis. Pulmonary tuberculosis is associated with decreased lymphocyte proliferative responses to mycobacterial Ags (4), reduced IL-2 secretion, and IL-2 receptor expression (5). A significant proportion of patients (17-25%) is unresponsive to purified protein derivative (PPD) 3 (6,7).…”

Tuberculosis Is Associated with a Down-Modulatory Lung Immune Response That Impairs Th1-Type Immunity

“…Despite the above observations, however, the preferred intracellular niche of M. tuberculosis remains the hostile phagolysosome of the alveolar macrophage (3,4). It is postulated that the suppressed responses to M. tuberculosis Ags in active TB (12,13) involves a suboptimal Th1-type response and ineffective macrophage activation.…”