Phenotype And Regulation Of IL-17-producing CD8+ T Lymphocytes In Tuberculous Pleural Effusion

Background:IL-17-producing CD8+ T lymphocytes (Tc17) cells have recently been detected in many cancers and autoimmune diseases. However, the possible implication of Tc17 cells in tuberculous pleural effusion remains unclarified. The objective of the present study was to explore the characterization of Tc17 cells present in pleural effusion of patients with tuberculous pleural effusion and investigate its possible role in the pathogenesis of TPE.Methods and Results:Distribution and phenotypic features of Tc17 cells in both tuberculous pleural effusion (TPE) and peripheral blood from patients with tuberculosis were determined by flow cytometry. We found that percentages of Tc17 cells were higher in TPE (1.75±0.16%), as compared to blood (0.79±0.08%), Tc17 cell frequency was correlated positively with Tc1 cell frequency (r= 0.549; p= 0.028) and Th17 cell frequency (r= 0.520; p= 0.039). Compared with IFN-γ-producing CD8+ T cells, Tc17 cells displayed higher expression of chemokine receptors (CCRs) and lower expression of cytotoxic molecules (CD107, Granzyme B and Perforin). In particularly, Tc17 cells in TPE exhibited high expression levels of CCR6, which could migrate in response to CCL20. Furthermore, IL-1β, IL-6, IL-23, or their various combinations could promote Tc17 cell expansion from CD8+ T cells, whereas the proliferative response of Te17 cells to above cytokines was lower than that of Th17 cells. The effects of local accessory cells (pleural mesothelial cells) on Tc17 cell expansion were also explored by ELISA. The transwell experiments showed that pleural mesothelial cells (PMCs) were able to stimulate Tc17 cell expansion via cell contact in an IL-1β/IL-6/IL-23 independent fashion.Conclusion:our study shows that Tc17 cells marks a subset of non-cytotoxic, CCR6+CD8+ T lymphocytes with poor proliferation ability and it may play a role in tuberculous pleural effusion. The overrepresentation of Tc17 cells in TPE may be due to Tc17 cell expansion stimulated by pleural proinflammatory cytokines and to recruitment of Tc17 cells from peripheral blood. Furthermore, CD8+ T cells can be induced to produce IL-17 via signals that other immunocytes provided. PMCs may promote the production of IL-17 by CD8+ T cells at sites of TPE via cell-cell interactions. Our data highlights the participation of PMCs in the course of CD8+ T cell responses, suggesting PMCs may be a critical target in control stimulation of Tc17 cells in TPE patients.