T-lymphocytes and pleural tuberculosis

Abstract

Development of monocyte-derived epithelioid cell granulomata in patients with pulmonary diseases such as tuberculosis, sarcoidosis and berylliosis provides direct evidence for the presence of heightened cellular immune responses in these patients. However, patients with these diseases often exhibit anergy to common recall antigens, suggesting a state of depressed cellular immune response. Partial resolution of this apparent paradox was obtained from studies in which the response of peripheral lymphocytes was compared to that of cells obtained from bronchoalveolar lavage sample or pleural fluid. Cells obtained from these latter two sources presumably are representative of cells present at the site of inflammation. These studies demonstrate several differences between the peripheral blood cells and those from the inflammatory sites. First, the cells from bronchoalveolar lavage or pleural fluid contained a significantly higher proportion of T-lymphocytes than comparable peripheral blood cells. Second, a greater proportion of the T-lymphocytes were helper T-lymphocytes in the bronchoalveolar lavage or pleural fluid cells, while the peripheral blood cells had an increased proportion of suppressor/cytotoxic T-lymphocytes. Third, the T-lymphocytes from bronchoalveolar lavage fluid spontaneously secreted significantly greater quantities of lymphokines (ie, monocyte chemotactic factor, macrophage activating factor, interleukin-1 and gamma-interferon), which are crucial to the formation and maintenance of the granuloma, than the peripheral blood cells did. Finally, the cells from bronchoalveolar lavage or pleural fluid exhibited a significantly greater proliferative response when challenged by the appropriate antigen (BeSO4 for berylliosis patients, PPD for tuberculosis patients) than was observed for the corresponding peripheral blood cells. From studies emerged the concept of 'compartmentalization,' which suggests that the responding T-lymphocytes have been partitioned from the peripheral blood to the site of inflammation. This concept provides a possible explanation for the observation that in vitro T-lymphocytes isolated from pleural fluid of patients with tuberculosis proliferate in response to PPD, while peripheral T-lymphocytes from the same patients do not. It is, however, clear that patients with advanced tuberculosis also have an increased number of suppressor cells in their peripheral blood. These suppressor cells could inhibit the proliferation of responding T-lymphocytes in the peripheral blood and thereby mask their presence. This study clearly demonstrates that the frequency of PPD-responding T-lymphocytes in tuberculosis patients is significantly greater in the pleural fluid than in their peripheral blood. However, the frequency in their peripheral blood is the same as that observed in the normal, tuberculin-positive patients. Although a limited number of patients were studied, the results obtained suggest that, at least for tuberculosis, the increased local cellular response is most likely due to clonal expansion of PPD-responding T-lymphocytes, and the decreased peripheral blood cellular immune response is most likely due to the action of suppressor cells rather than the migratory loss of PPD-responding T-lymphocytes from blood to the inflammation site. The activity of suppressor cells on B-lymphocytes may also reduce the humoral immune response to mycobacterial antigens and, along with other factors, frustrate efforts to develop a reliable serologic test for tuberculosis. The search for useful serologic tests in the diagnosis of tuberculosis will and should continue. Nevertheless, as our understanding of useful events at the inflammatory site improves, perhaps in time these observations will also have diagnostic significance.