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.

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.

Background N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker useful in diagnosis of pleural effusion due to heart failure. Thus far, its overall diagnostic accuracy has not been systematically reviewed. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of the measurement of pleural NT-proBNP for identifying pleural effusion due to heart failure. Methods After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of NT-proBNP concentrations in pleural fluid in the diagnosis of pleural effusion resulting from heart failure were pooled using fixed-effects models. Summary receiver operating characteristic curves were used to summarise overall test performance. Results Eight publications met the inclusion criteria. The summary estimates for pleural NT-proBNP in the diagnosis of pleural effusion attributable to heart failure were: sensitivity 0.95 (95% CI 0.92 to 0.97), specificity 0.94 (0.92 to 0.96), positive likelihood ratio 14.12 (10.23 to 19.51), negative likelihood ratio 0.06 (0.04 to 0.09) and diagnostic OR 213.87 (122.50 to 373.40). Conclusions NT-proBNP levels in pleural fluid showed a high diagnostic accuracy and may help accurately differentiate cardiac from non-cardiac conditions in patients presenting with pleural effusion.

Cytotoxic lymphocyte associated antigen-4 (CTLA-4) is a homologue of CD28, which plays a critical role in the down-regulation of antigenactivated immune response. The aim of the present study was to investigate the concentrations of soluble CTLA-4 in sera of patients with bronchial asthma and the correlation between soluble CTLA-4 concentrations and some clinical measures of asthma. The concentrations of serum soluble CTLA-4 in 31 atopic asthmatics, 20 non-atopic asthmatics, and 28 non-atopic normal control volunteers were determined by ELISA technique, and the relationship between serum soluble CTLA-4 concentrations in asthmatics and airway responsiveness, pulmonary function, blood white cell counts and differentials, respectively, were analyzed. Serum soluble CTLA-4 concentrations in both atopic asthmatics (20.2

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.