Acute tropical pulmonary eosinophilia. Characterization of the lower respiratory tract inflammation and its response to therapy.

Although acute tropical pulmonary eosinophilia (TPE) is well recognized as a manifestation of filarial infection, the processes that mediate the abnormalities of the lung in TPE are unknown. To evaluate the hypothesis that the derangements of the lower respiratory tract in this disorder are mediated by inflammatory cells in the local milieu, we utilized bronchoalveolar lavage to evaluate affected individuals before and after therapy. Inflammatory cells recovered from the lower respiratory tract of individuals with acute, untreated TPE (n = 8) revealed a striking eosinophilic alveolitis, with marked elevations in both the proportion of eosinophils (TPE 54 +/- 5%; normal 2 +/- 5%; P less than 0.001) and the concentration of eosinophils in the recovered epithelial lining fluid (ELF) (TPE 63 +/- 20 X 10(3)/microliter; normal 0.3 +/- 0.1 X 10(3)/microliter; P less than 0.01). Importantly, when individuals (n = 5) with acute TPE were treated with diethylcarbamazine (DEC), there was a marked decrease of the lung eosinophils and concomitant increase in lung function. These observations are consistent with the concept that at least some of the abnormalities found in the lung in acute TPE are mediated by an eosinophil-dominated inflammatory process in the lower respiratory tract.

Serum lactate dehydrogenase activity in patients with AIDS and Pneumocystis carinii pneumonia. An adjunct to diagnosis.

We investigated whether serum lactate dehydrogenase activity (LD) is significantly elevated in patients with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) when compared to patients with non-Pneumocystis pneumonia. We measured LD (U/L), blood total lymphocyte count (1,000/cu mm), and alveolar-arterial oxygen tension difference P(A-a)O2 (mm Hg), in 30 patients with AIDS and PCP (group 1), four patients with AIDS or AIDS-related complex (ARC) and non-Pneumocystis pneumonia (NPCP) (group 2), and seven patients with pneumococcal pneumonia and bacteremia (PPB) (group 3). In patients with AIDS and PCP, LD was 509 +/- 35 (mean +/- SE), which was significantly elevated in comparison to both AIDS/ARC patients with NPCP (228 +/- 21) (p less than .001), and patients with PPB (211 +/- 21) (p less than .001). There was a significant positive correlation between LD and P(A-a)O2 (r = .51, p = 0.01). P(A-a)O2 was markedly elevated in both AIDS patients with PCP (48 +/- 3), and patients with pneumococcal pneumonia (44 +/- 3), but only moderately elevated in AIDS/ARC patients with NPCP (29 +/- 6). These results suggest that measurement of LD may be useful in differentiating Pneumocystis pneumonia from non-Pneumocystis pneumonia. In addition, the increase in LD correlates with the degree of pulmonary oxygen transfer abnormality.

Analysis of induced sputum in the diagnosis of Pneumocystis carinii pneumonia.

Sixty-two patients with possible AIDS-associated Pneumocystis carinii pneumonia (PCP) were studied to determine the diagnostic usefulness of sputum analysis and whether or not the results of sputum analysis are related to severity of disease. Induced sputum was stained with Gomori Methenamine silver and modified Wright Giemsa stains. Indicators of disease severity were: extent of chest roentgenographic infiltrate, serum lactic dehydrogenase activity, alveolar-arterial oxygen tension difference, and total blood lymphocyte count. All patients with sputum negative for Pneumocystis underwent bronchoscopy with bronchoalveolar lavage. Sputum analysis was 71% sensitive and 100% specific for the diagnosis of PCP. The negative predictive value of sputum analysis was 48%. There was no relationship between sputum results and the severity of PCP. This study led to the conclusions that sputum analysis is a sensitive, specific, rapid, and low-cost technique for the diagnosis of PCP, and that the sensitivity of sputum analysis for the detection of PCP is not affected by the severity of PCP.

Case report: hepatic hydrothorax without ascites.

Pleural effusion due to hepatic cirrhosis and ascites is well known. We describe three patients with right-sided hepatic hydrothorax in the absence of ascites. The formation of pleural fluid in these patients is probably a result of fluid movement from peritoneal to pleural space across diaphragmatic defects before ascites can form. The differential diagnosis of a right-sided transudative pleural effusion in a patient with chronic liver disease with or without ascites includes congestive left ventricular failure and nephrotic syndrome. These diseases are usually ruled out with standard clinical tests. Patients with hepatic hydrothorax should be treated with fluid restriction and diuretics. Patients with severe symptoms due to refractory hepatic hydrothorax might benefit from pleural sclerosis and surgical closure of diaphragmatic defects.

Studies on the autologous MLR in primary biliary cirrhosis: evidence that the autologous MLR is a negative feedblock response stimulated by activated B cells.

Patients with primary biliary cirrhosis (PBC) were found to have diminished suppression of pokeweed mitogen (PWM)-stimulated immunoglobulin synthesis by in vitro cultures containing autologous T and B cells. The possibility that this abnormality is due to a defect of autologous cell-cell interactions was suggested by the finding that patients with PBC have a significantly diminished proliferative response in the autologous mixed lymphocyte reaction (MLR). In studies of normal lymphocytes, it was found that T cells activated in the autologous MLR have the capacity to suppress PWM-stimulated immunoglobulin synthesis, but do not have augmented helper function. Furthermore, when T cells were activated with lymphoblastoid B cells, augmented suppressor activity was observed. These findings suggest that the autologous MLR represents a negative feedback loop in which activated B cells initiate a suppressor T cell pathway. The defect in the autologous MLR in patients with PBC may account for the diminished suppressor cell function observed in this disease.

The role of the transferrin receptor in human B lymphocyte activation.

Transferrin receptors are expressed on proliferating cells and are required for their growth. Transferrin receptors can be detected after, but not before, mitogenic stimulation of normal peripheral blood T and B cells. T cells demonstrate a functional requirement for transferrin receptors in the activation process. These receptors, in turn, are induced to appear by T cell growth factor (interleukin 2). In the experiments reported here, we examined the regulation of transferrin receptor expression on activated human B cells and whether these receptors are necessary for activation to occur. Activation was assessed by studying both proliferation and immunoglobulin secretion. We determined that transferrin receptor expression on B cells is regulated by a factor contained in supernatants of mitogen-stimulated T cells (probably B cell growth factor). This expression is required for proliferation to occur, because antibody to transferrin receptor (42/6) blocks B cell proliferation. Induction of immunoglobulin secretion, however, although dependent on phytohemagglutinin-treated T cell supernatant, is not dependent on transferrin receptor expression and can occur in mitogen-stimulated cells whose proliferation has been blocked by anti-transferrin receptor antibody. These findings support a model for B cell activation in which mitogen (or antigen) delivers two concurrent but distinct signals to B cells: one, dependent on B cell growth factor and transferrin receptor expression, for proliferation; and a second, dependent on T cell-derived factors and not requiring transferrin receptors, which leads to immunoglobulin secretion.

Immunoregulatory function of T cells activated in the autologous mixed lymphocyte reaction.

This study was undertaken to define the functional properties of T cells stimulated in the autologous mixed lymphocyte reaction (MLR) by purified B cells or macrophages. In preliminary experiments, it was found that T cells that had been cultured with autologous non-T cells inhibited pokeweed mitogen- (PWM) stimulated immunoglobulin synthesis by autologous B cells. In addition, the T cell-mediated suppression was eliminated by x-irradiation and hydrocortisone treatment, was mediated by a mechanism that occurred early in the PWM-stimulated cultures, and did not involve killing of mature immunoglobulin-secreting cells. T cells were then cultured with either autologous B cells or macrophages in order to determine whether such autoreactive T cells had a similar capacity to regulate PWM-induced immunoglobulin synthesis. Although T cell populations stimulated either by B cells or by macrophages suppressed proliferative responses and immunoglobulin synthesis, both these populations of autoreactive T cells provided help for immunoglobulin synthesis that was not significantly different from that provided by fresh T cells. These results suggest that the predominant functional consequence of activation of T cells in the autologous MLR is the generation of suppressor T cells capable of inhibiting immunoglobulin synthesis. Thus, the autologous MLR may represent a negative feedback mechanism for the regulation of the immune response.

Respiratory failure due to a massive rheumatoid pleural effusion.

A patient with rheumatoid arthritis (RA) and chronic obstructive lung disease was admitted with respiratory failure due to a massive pleural effusion. An extensive evaluation proved the effusion to be of rheumatoid origin. The effusion resolved with prednisone and penicillamine therapy. Although pleural effusions associated with RA are common, massive effusions are rare and respiratory failure from a rheumatoid pleural effusion has not been reported.

Transferrin receptor induction is required for human B-lymphocyte activation but not for immunoglobulin secretion.

Transferrin receptors are expressed on proliferating cells and are required for their growth. Transferrin receptors can be detected after, but not before, mitogenic stimulation of normal peripheral blood T and B cells. In the experiments reported here we have examined the regulation of transferrin receptor expression on activated human B cells and whether or not these receptors are necessary for activation to occur. Activation was assessed by studying both proliferation and immunoglobulin secretion. We have determined that transferrin receptor expression on B cells is regulated by a factor contained in supernatants of mitogen-stimulated T cells (probably B-cell growth factor). This expression is required for proliferation to occur, since antibody to transferrin receptor (42/6) blocks B-cell proliferation. Induction of immunoglobulin secretion, however, although dependent on PHA-treated T-cell supernatant, is not dependent on transferrin receptor expression and can occur in mitogen-stimulated cells whose proliferation has been blocked by antitransferrin receptor antibody. In addition, we have demonstrated that IgM messenger RNA induction following mitogen stimulation is unaffected by antitransferrin receptor antibody. These findings support a model for B-cell activation in which mitogen (or antigen) delivers two concurrent but distinct signals to B cells: one, dependent on B-cell growth factor and transferrin receptor expression, for proliferation, and a second, dependent on T cell-derived factors and not requiring transferrin receptors, which leads to immunoglobulin secretion.

Pleuropulmonary manifestations of hepatic amebiasis.

Pleuropulmonary manifestations of hepatic amebiasis occurred in 30 patients; 18 (60%) presented with at least 1 pulmonary complaint and 10 (33%) had multiple pulmonary symptoms. In 14 patients (47%), abnormalities were found on examination of the chest. In 16 chest roentgenograms (53%), there was at least 1 abnormality: right-sided pleural effusion (9 patients) and elevated right hemidiaphragm (8 patients) were the most common. All patients were treated with metronidazole (Flagyl) and had resolution of the amebic liver abscess and pulmonary disease. Pleuropulmonary disease is a common complication of amebic liver abscess. The clinical presentation and chest roentgenograms are virtually diagnostic and obviate the need for invasive procedures to confirm the diagnosis. Pleuropulmonary disease resolves with amebicidal treatment of the hepatic abscess.

An autoreactive T cell clone that can be activated to provide both helper and suppressor function.

To understand further the biologic significance of the autologous mixed lymphocyte reaction, we determined the functional properties of autoreactive T cell lines and clones. Initially, we found that cells in an uncloned autoreactive Leu-3+ T cell line helped immunoglobulin production when added to cultures containing fresh T and non-T cells in the absence of pokeweed mitogen (PWM) but suppressed immunoglobulin production in the same cultures in the presence of PWM. To explain this phenomenon, we studied the immunoregulatory potential of an autoreactive T cell clone termed MTC-4. This clone bore the phenotype Leu-3+, 2-, 8-, 11-, DR+ and underwent proliferation when co-cultured with autologous, but not allogeneic non-T cells. Of interest, the immunoregulatory potential of the MTC-4 cells varied according to how the cells were activated. When MTC-4 cells were cultured with autologous non-T cells in the absence of antigen or mitogen (unactivated non-T cells), polyclonal immunoglobulin production (detected by reverse PFC assay) was observed. This helper activity was MHC-restricted in that it was elicited only by autologous non-T cells or MHC-matched allogeneic non-T cells; however, once activated by autologous non-T cells, it could also help allogeneic non-T cells. In contrast, when MTC-4 cells were cultured with autologous non-T cells in the presence of PWM (activated non-T cells), immunoglobulin production was greatly suppressed. This suppression was also observed when MTC-4 cells were added to cultures containing exogenous T cell help (such as that provided by autologous fresh T cells) and was not due to a direct effect of PWM on the T cell clone, because preincubation of MTC-4 cells with PWM before culture with non-T cells did not result in suppression. On the basis of these data, we conclude that autoreactive T cells can have dual immunoregulatory function that is manifest, at least in part, at the single cell level. Moreover, these regulatory functions are differentially elicited depending on the state of activation of the stimulating autologous non-T cells: when stimulated by MHC antigens present on unactivated B cells, they provide helper activity; and when stimulated by MHC antigens present on activated B cells, they act as suppressor cells. Autoreactive T cells with dual regulatory potential appear to make up a substantial proportion of all autoreactive T cells and are cells that are uniquely adapted to maintain immunologic homeostasis.