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.

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.

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.

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.

Background: Previous studies have reported that soluble (s) CD86 is involved in the initiation of the immune response. A study was undertaken to investigate the concentrations of sCD86 in serum samples from patients with bronchial asthma and to determine the cell origin of sCD86. Methods: Serum sCD86 concentrations were measured in 52 asthmatic subjects and 25 non-atopic normal volunteers using an enzyme linked immunosorbent assay, and the relationship of serum sCD86 concentrations to asthma severity and to total and differential white cell counts was analysed. Each type of white blood cell was purified and cultured in vitro to determine the cell origin of serum sCD86. Results: Serum samples from patients with an acute asthma exacerbation had much higher levels of sCD86 (585.4 (20.5)IU/ml) than those from stable asthmatics (479.6 (15.7)IU/ml, p,0.001) and healthy individuals (435.1 (13.8)IU/ml, p,0.001), and there was no difference between the latter two groups (p=0.079). In asthmatic subjects the serum sCD86 level was inversely correlated with airway responsiveness, forced expiratory volume in 1 second, and with arterial carbon dioxide tension. In addition, the serum sCD86 level was positively correlated with numbers of lymphocytes, eosinophils, monocytes, but not neutrophils. The in vitro experiments indicated that sCD86 was produced by monocytes. Conclusions: The serum sCD86 protein level was significantly increased in asthmatic subjects during an exacerbation and correlated with the severity of asthma. sCD86 is most probably derived from monocytes in the peripheral blood.