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CD 8 + T cells with distinct cytokine‐producing features and low cytotoxic activity in eosinophilic and non‐eosinophilic chronic rhinosinusitis with nasal polyps
Author(s) -
Ma J.,
Shi L.L.,
Deng Y.K.,
Wang H.,
Cao P.P.,
Long X.B.,
Zhang X.H.,
Liu Y.,
Zeng M.,
Liu Z.
Publication year - 2016
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12758
Subject(s) - cytotoxic t cell , granzyme b , perforin , granzyme , immunology , nasal polyps , eosinophil , eosinophilia , t cell , eosinophilic , chemokine , granzyme a , interleukin 5 , cytokine , biology , medicine , microbiology and biotechnology , immune system , interleukin , cd8 , pathology , biochemistry , asthma , in vitro
Summary Background CD 8 + T cells are important effectors of cell‐mediated immunity; however, their contribution to the pathogenesis of CRS is unclear. Objective This study aimed to characterize the cytokine‐producing features and cytotoxic activity of CD 8 + T cells, and their correlation with inflammation patterns in CRS with nasal polyps. Methods The expression of IFN ‐γ, IL ‐4, IL ‐5, IL ‐17A, forkhead box P3 ( FOXP 3), perforin, and granzyme B in CD 8 + T cells was studied by means of flow cytometry, immunohistochemistry, and immunofluorescence. The expression of CD 8 + T‐cell subset relevant chemokines and chemokine receptors was detected by means of real‐time RT ‐ PCR or ELISA . The cytotoxic activity of sorted CD 8 + T cells was defined by anti‐ CD 3‐redirected killing assay. Results Compared with controls, elevated percentages of total CD 8 + T cells and cytotoxic T lymphocyte (Tc) 1 ( IFN ‐γ + ), Tc2 ( IL ‐4 + ), and Tc17 ( IL ‐17A + ) cell subset, and decreased percentages of FOXP 3 + CD 8 + 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 CD 8 + T cells were found to produce similar or even higher levels of IFN ‐γ and IL ‐4 compared with CD 4 + 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 CD 8 + T cells compared with their counterparts in peripheral blood. The expression of CXCL 16, CCL 17, and CCL 20 positively correlated with Tc1, Tc2, and Tc17 cell subset number in sinonasal mucosa, respectively. Conclusion and Clinical Relevance CD 8 + 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.