IL-17–producing CD4+ T (Th17) cells have been found to be increased in some human cancers; however, the possible implication of Th17 cells in regulating antitumor responses in malignant pleural effusion (MPE) remains to be elucidated. In the current study, distribution and phenotypic features of Th17 cells in both MPE and peripheral blood from patients with lung cancer were determined by flow cytometry or double immunofluorescence staining. The impacts of cytokines on Th17 cell generation and differentiation were explored. The chemoattractant activity of chemokines CCL20 and CCL22 for Th17 cells in vitro was also observed. It was found that the increased Th17 cells could be found in MPE compared with blood. The in vitro experiments showed that IL-1b, IL-6, IL-23, or their various combinations could promote Th17 cell generation and differentiation from naive CD4+ T cells. MPE was chemotactic for Th17 cells, and this activity was partly blocked by anti-CCL20 and/or CCL22 Abs. Our data also showed that the accumulation of Th17 cells in MPE predicted improved patient survival. It could be concluded that the overrepresentation of Th17 cells in MPE might be due to Th17 cell differentiation and expansion stimulated by pleural proinflammatory cytokines and to recruitment of Th17 cells from peripheral blood induced by pleural chemokines CCL20 and CCL22. Furthermore, the accumulation of Th17 cells in MPE predicted improved patient survival. These data provide the basis for developing immune-boosting strategies based on ridding the cancer patient of this cell population. The Journal of Immunology,

The aim of this study was to investigate the presence of epithelial neutrophil-activating peptide (ENA)-78 in pleural effusions, as well as the chemoattractant activity of pleural ENA-78 0n neutrophils. Pleural effusion and serum samples were collected from 75 patients who presented to the respiratory institute (19 with malignant pleural effusion, 21 with tuberculous pleural effusion, 18 with infectious pleural effusion and 17 with transudative pleural effusion). The concentrations of ENA-78, myeloperoxidase and neutrophil elastase were determined, and the chemoattractant activity of ENA-78 for neutrophils both in vitro and in vivo was also observed. The concentrations of ENA-78, myeloperoxidase and neutrophil elastase in infectious pleural effusion were significantly higher than those in malignant, tuberculous and transudative groups, respectively (all p<0.01). Infectious pleural fluid was chemotactic for neutrophils in vitro and anti-ENA-78 antibody could partly inhibit these chemotactic effects. Intrapleural administration of ENA-78 produced a marked progressive influx of neutrophils into pleural space. Compared with noninfectious pleural effusion, ENA-78 appeared to be increased in infectious pleural effusion. Our data suggested that ENA-78 was able to induce neutrophil infiltration into pleural space and might be responsible for pleural neutrophil degranulation.

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.