Reduced Th17 Response in Patients with Tuberculosis Correlates with IL-6R Expression on CD4+ T Cells

Rationale: Although it is well recognized that CD4(+) T cells and T helper (Th) 1 cytokines are critical in the cell-mediated response to Mycobacterium tuberculosis, it is also clear that this immunity alone is not enough. Understanding the roles of other T cell subsets and cytokines is essential for vaccine design and clinical immunotherapy against tuberculosis (TB). Objectives: To investigate the clinical significance and possible regulatory mechanism of Th 1 7 responses in human TB. Methods: The frequencies of IFN-gamma-, IL-4-, IL-17-, FoxP3- and IL-6 receptor (IL-6R)-expressing CD4(+) T cells in blood and/or pleural effusion samples of healthy donors, subjects with latent TB infection, and patients with active TB were analyzed by flow cytometry. Cytokines, transforming growth factor-beta and IL-6, in plasma and pleural fluid samples were determined by ELISA. Measurements and Main Results: The frequency of Th17 cells in patients with active TB is significantly lower than those in healthy donors and individuals with latent TB infection. Correlation analysis showed that reduced Th17 responses observed in patients with active TB was significantly correlated with the decreased expression of IL-6R on CD4(+) T cells, but did not correlate with the concentrations of the cytokines, transforming growth factor-beta and IL-6. Consistently; in vitro study showed that M. tuberculosis products inhibit the expression of IL-6R on CD4(+) T cells. Conclusions: Our results demonstrate that reduced Th17 responses were associated with the clinical outcome of M. tuberculosis infection. Suppression of Th17 response through down-regulation of IL-6R expression may be an important mechanism in the development of active TB.