Abstract
Silicosis is a fibrosing lung disease induced by silica particle inhalation. In addition to its effects on pulmonary physiology, the disease is also associated with clinically important immune dysfunction, detectable both systemically and in the lung. An important local pulmonary manifestation of silicosis-associated immune dysfunction is impaired host defense against mycobacteria. Normal host defense against mycobacteria is accomplished through cell-mediated responses by T cells and macrophages. The mechanism underlying impaired antimycobacterial defense and silicotuberculosis in silicotics is unknown. Despite impaired host defense against mycobacteria, silicosis appears to be associated with increased and dysregulated antibody production, as evidenced by the presence of hypergammaglobulinemia, circulating immune complexes, and autoantibodies in many patients with silicosis. The apparent paradox of excess antibody production, but impaired cell-mediated immunity, is not unique to silicosis. In a variety of strong immune responses, antibody production and delayed-type hypersensitivity responses are mutually exclusive. In these settings, the underlying mechanism for up-regulation of one type of response and down-regulation of the other type has been regulation and cross-regulation by helper T (TH)-cell subsets. Based on cytokine secretion patterns, two types of CD4+ T-cell subsets have recently been identified—TH1 and TH2. TH2-cell-like responses are associated with strong antibody production, while TH1-cell-like responses are associated with delayed-type hypersensitivity. Each TH cell type is capable of down-regulating the other. We hypothesize that dysregulated TH cell interactions occur in silicosis, resulting in augmentation of antibody responses, and suppression of cell-mediated immunity.