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.

Costimulatory molecules are cell surface glycoproteins that can direct, modulate and fine-tune T-cell receptor signals. The B7-1/B7-2-CD28/CTLA-4 and ICOS-B7RP-1 pathway provides key second signals that can regulate the activation, inhibition and fine-tuning of T-lymphocyte responses. The expression of B7-1/ B7-2-CD28/CTLA-4 molecules on clinical samples from patients with asthma have been well studied, and the results indicate that different extents of these molecules are expressed on the surface of various cells, and that the concentrations of soluble form of these molecules are elevated in the sera of patients with asthma. There is a burst of papers describing an important role for B7-1/B7-2-CD28/CTLA-4 pathway in the Th1/Th2 balance. Similarly, ICOS stimulates both Th1 and Th2 cytokine production but may have a preferential role in Th2 cell development. Moreover, The B7-1/B7-2-CD28/CTLA-4 and ICOS-B7RP-1 pathway has been suggested of being involved in the development of airway inflammation and airway hyperresponsiveness. Further study of the functions of the pathways within the CD28/CTLA-4-CD80/CD86 and ICOS-B7RP-1 superfamily individually and their interplay should provide insights into the pathogenesis of asthma, and has great therapeutic potential for treatment of asthma.

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.

Active suppression by CD4+CD25+ regulatory T lymphocytes plays an important role in the downregulation of T-cell responses to foreign and self-antigens. Objective: To analyze whether the CD4+CD25+ regulatory T lymphocytes exist and function normally in malignant pleural effusion. Methods: The percentages of CD4+CD25+ T lymphocytes in pleural effusion and peripheral blood from patients with lung cancer with malignant effusion, pleural lavage and peripheral blood from patients with lung cancer without effusion, and peripheral blood from healthy control subjects were determined by flow cytometry. The expressions of forkhead transcription factor Foxp3 and cytotoxic lymphocyte-associated antigen-4 were also examined. CD4+CD25+ and CD4+CD25- T cells from pleural effusion and peripheral blood were isolated, and were cultured to observe the effects of CD4+CD25+ cells on proliferation response of CD4+CD25- T cells in vitro. Main Results: There were increased numbers of CD4+CD25+ T cells In malignant pleural effusion from patients with lung cancer compared with pleural lavage from patients with lung cancer without pleural effusion, and that these cells have constitutive high-level expression of Foxp3 and cytotoxic lymphocyte-associated antigen-4. Furthermore, CD4+CD25+ T cells mediate potent inhibition of proliferation response of CD4+CD25- T cells, and anticytotoxic lymphocyte-associated antigen-4 monoclonal antibody could reduce the inhibitory activity of CD4+CD25+ T cells. Conclusions: The increased CD4+CD25+ T cells found in malignant pleural effusion express high levels of Foxp3 transcription factor and potently suppress the proliferation of CD4+CD25- T cells, and cytotoxic lymphocyte-associated antigen-4 is involved in the suppressive activity of pleural CD4+CD25+ T cells.