Purpose: The aim of this study was to explore the presence of the chemokines CCL22 and CCL17 in malignant pleural effusion, and the chemoattractant activity of these chemokines on CD4-positive CD25-positive Foxp3-positive reg ulatory Tcells infiltrating into the pleural space. Experimental Design: The concentrations of CCL22 and CCL17 in both pleural effusions and sera from 33 patients with lung cancer were determined. Flow cytometry was done to determine T lymphocyte subsets in cell pellets of pleural effusion. Pleural cells were analyzed for the expres-sion of CCL22 and CCL17. The chemoattractant activity of CCL22 for regulatory Tcells in vitro and in vivo was also observed. Results: The concentration of CCL22 in malignant pleural effusion was significantly higher than that in the corresponding serum. Pleural fluid from lung cancer patients was chemotactic for reg-ulatoryTcells, and this activity was partly blocked by an anti-CCL22, but not by an anti-CCL17 antibody. Intrapleural administration of CCL22 0f patients produced a marked progressive influx of reg ulatory T cells into pleural space. Conclusions: Compared with serum, CCL22 seemed to be increased in malignant pleural effu-sion, and could directly induce reg ulatory T cell infiltration into the pleural space in patients with malignant effusion.

Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of interferon (IFN)-γ measurements in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a metaanalysis to determine the accuracy of IFN-γ measurements in the diagnosis of tuberculous pleurisy. Methods: After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of IFN-γ concentrations in the diagnosis of pleural effusion were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Results: Twenty-two studies met our inclusion criteria. The summary estimates for IFN-γ in the diagnosis of tuberculous pleurisy in the studies included were as follows: sensitivity, 0.89 (95% confidence interval [CI], 0.87 to 0.91); specificity, 0.97 (95% CI, 0.96 to 0.98); positive likelihood ratio, 23.45 (95% CI, 17.31 to 31.78); negative likelihood ratio, 0.11 (95% CI, 0.07 to 0.16); and diagnostic odds ratio, 272.7 (95% CI, 147.5 to 504.2). Conclusions: IFN-γ determination is a sensitive and specific test for the diagnosis of tuberculous pleurisy. The measurement of IFN-γ levels in pleural effusions is thus likely to be a useful tool for diagnosing tuberculous pleurisy. The results of IFN-γ assays should be interpreted in parallel with clinical findings and the results of conventional tests. (CHEST 2007; 131:1133–1141)

Study objective: To investigate the effects of segmental allergen challenge on the concentration of soluble CD86 (sCD86) in BAL fluids in patients with allergic asthma. Methods: BAL fluid and peripheral blood were collected at baseline, 24h after segmental saline solution or allergen challenge by fiberoptic bronchoscopy and venepuncture, respectively, from 10 patients with allergic asthma. Total and differential cell counts in BAL fluid were performed, and sCD86 levels in both BAL fluid and serum were measured by enzyme-linked immunosorbent assay. Results: In allergic asthmatics, there was no significant increase in BAL sCD86 concentrations after saline solution challenge (median, 2.0IU/L; 25th to 75th percentiles, 0 to 3.4) compared with baseline control subjects (median, 1.2IU/L; 25th to 75th percentiles, 0 to 3.6IU/mL; p 0.735); however, sCD86 concentrations were significantly elevated after allergen challenge (median, 8.1IU/L; 25th to 75th percentiles, 4.4 to 17.0IU/mL; p<0.001). The concentrations of sCD86 in BAL fluid after allergen challenge exceeded levels that could be accounted for passive transudation from the circulation, based on the magnitude of increases in BAL albumin concentrations. Conclusions: These data indicate that allergen challenge results in a significant local accumulation of sCD86 within the airways, and that the local release of sCD86 may play a role in allergen-induced inflammatory processes in the asthmatic airways.

Allergic asthma is characterized by airway hyper-responsiveness and chronic mucosal inflammation mediated by CD4+ Th2 lymphocytes. Regulatory CD4+CD25+ T cells are important components of the homeostasis of the immune system, as impaired CD4+CD25+ T cell activity can cause autoimmune diseases and allergy. The mechanism of suppression by CD4+CD25+ T cells remains controversial; different in vivo and in vitro studies raise possible roles for the immunosuppressive cytokines interleukin-10 and transforming growth factor-β, forkhead transcription factor Foxp3, glucocorticoid-induced tumor necrosis factor receptor, cytotoxic lymphocyte associated antigen-4, 4-1BB costimulator receptor, a CD4-related molecule LAG-3, and neuropilin-1. Current data suggest that Th2 responses to allergens are normally suppressed by CD4+CD25+ T cells. Suppression by CD4+CD25+ T cells is decreased in allergic individuals. Furthermore, CD4+CD25+ T cells play a key role in regulating airway eosinophilic inflammation. The immunomodulatory properties of CD4+CD25+ T cells do extend to Th2 responses, most notably by limiting the development of a proinflammatory CD4+ Th2 phenotype characterized by reduced cytokine production. An understanding of the roles of CD4+CD25+ T cells in vivo could provide better insight into the design of novel approaches to modulate the chronic airway inflammatory reaction evident in bronchial asthma.