CD8+ T cells with distinct cytokine‐producing features and low cytotoxic activity in eosinophilic and non‐eosinophilic chronic rhinosinusitis with nasal polyps

Abstract

CD8(+) T cells are important effectors of cell-mediated immunity; however, their contribution to the pathogenesis of CRS is unclear. This study aimed to characterize the cytokine-producing features and cytotoxic activity of CD8(+) T cells, and their correlation with inflammation patterns in CRS with nasal polyps. The expression of IFN-γ, IL-4, IL-5, IL-17A, forkhead box P3 (FOXP3), perforin, and granzyme B in CD8(+) T cells was studied by means of flow cytometry, immunohistochemistry, and immunofluorescence. The expression of CD8(+) T-cell subset relevant chemokines and chemokine receptors was detected by means of real-time RT-PCR or ELISA. The cytotoxic activity of sorted CD8(+) T cells was defined by anti-CD3-redirected killing assay. Compared with controls, elevated percentages of total CD8(+) T cells and cytotoxic T lymphocyte (Tc) 1 (IFN-γ(+) ), Tc2 (IL-4(+) ), and Tc17 (IL-17A(+) ) cell subset, and decreased percentages of FOXP3(+) CD8(+) regulatory T cells, were found in both eosinophilic and non-eosinophilic polyps with a Tc2-skewed and Tc1/Tc17-dominated response in eosinophilic and non-eosinophilic polyps, respectively. Nasal CD8(+) T cells were found to produce similar or even higher levels of IFN-γ and IL-4 compared with CD4(+) T cells. Tc1 and Tc17, and Tc2 (IL-4(+) and IL-5(+) ) cell subset percentages positively correlated with neutrophil and eosinophil counts in sinonasal mucosa, respectively. Strikingly, the expression of perforin and granzyme B and cytotoxic activity were significantly reduced in nasal CD8(+) T cells compared with their counterparts in peripheral blood. The expression of CXCL16, CCL17, and CCL20 positively correlated with Tc1, Tc2, and Tc17 cell subset number in sinonasal mucosa, respectively. CD8(+) T cells have low cytotoxic activity; nevertheless, they are a significant and previously underappreciated source of inflammatory cytokine production in polyps. Different Tc cell subset domination may contribute to distinctly biased granulocyte inflammation in eosinophilic and non-eosinophilic polyps.