Font Size: a A A

CD8~+ T Cells With Distinct Cytokine Producing Features And Low Cytotoxic Activity In Eosinophilic And Non-eosinophilic Chronic Rhinosinusitis With Nasal Polyps

Posted on:2017-03-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:J MaFull Text:PDF
GTID:1314330482994314Subject:Otorhinolaryngology
Abstract/Summary:PDF Full Text Request
Background:CD8+T cells are important effectors of cell-mediated immunity. Although increased accumulation of CD8+T cells has been demonstrated in chronic rhinosinusitis (CRS), their precise role in the pathogenesis of CRS is unclear.This study aimed to characterize the cytokine producing feature and cytotoxic activity of CD8+T cells, and their correlation with inflammation patterns in CRS with nasal polyps.Methods:IFN-y, IL-4 and IL-17A, and perforin and granzyme B expression in CD8+ T cells were studied by means of flow cytometry and immunohistochemistry. 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.Results:Compared with controls, elevated percentages of total CD8+T cells and cytotoxic T lymphocyte (Tc) 1 (IFN-?+), Tc2 (IL-4+) and Tc17 (IL-17A+) cell subset were found in both eosinophilic and non-eosinophilic polyps with a further 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-? and IL-4 as compared with CD4+T cells. Tc1 and Tc17, and Tc2 cell subset percentages positively correlated with neutrophil and eosinophil counts in sinonasal mucosa, respectively. Strikingly, perforin and granzyme B expression and cytotoxic activity were significantly reduced in nasal CD8+T cells compared with their counterparts in peripheral bloods. The expression of CXCL16, CCL17 and CCL20 positively correlated with Tel, Tc2 and Tc17 cell subset number in sinonasal mucosa, respectively.Conclusion:CD8+T cells have a low cytotoxic activity; nevertheless, they are a significant and previously unappreciated source of inflammatory cytokine production in polyps. Different Tc cell subset domination may contribute to distinct biased granulocyte inflammation in eosinophilic and non-eosinophilic polyps.
Keywords/Search Tags:chronic rhinosinusitis, cytokine, cytotoxic T lymphocyte, cytotoxity, eosinophil, neutrophil, nasal polyps
PDF Full Text Request
Related items