The objective of the present study was to figure out whether human IL-27-producing CD4⁺ T cells represent a distinct T cell subset in tuberculosis pleural effusion (TPE).

Distribution, phenotypic features of IL-27-producing CD4⁺ T cells in TPE were determined. The required transcription factors and signal transductions for IL-27-producing CD4⁺ T cell differentiation were explored. The immune regulation of IL-27 on pleural mesothelial cells was observed.

We have determined the presence of a subset of human Th cells that infiltrated into tuberculous pleural effusion, which was characterized by the secretion of IL-27, and somehow IFN-γ, but not of IL-4, IL-9, IL-17, or IL-22. These IL-27-producing CD4⁺ T cells were effector memory cells and exhibited a transcription profile clearly separated from those of Th2, Th17, Th9, and Th22 cells. The in vitro experiments showed that IL-1β, IL-2 and IL-12, or their various combinations could promote IL-27⁺CD4⁺ T cell differentiation from naive CD4⁺ T cells by means of phosphorylation of STAT3, STAT4, or/and STAT5. Transcription factors c-Fos and T-bet were required for IL-27⁺CD4⁺ T cell differentiation. By activating STAT3 signaling, IL-27 not only restored a clear epithelial phenotype of pleural mesothelial cells, but also further reversed IFN-γ-induced epithelial–mesenchymal transition of pleural mesothelial cells.

These data suggested that human IL-27⁺CD4⁺ T cells might represent a distinct human T cell subset with unique expression profiles of transcription factors and proinflammatory cytokines, and these IL-27⁺CD4⁺ T cells may play important roles in tuberculosis immunity by affecting pleural mesothelial cells.