Effects of cigarette smoke on killer cell activation in chronic obstructive pulmonary disease

Wang, Jia (2015) Effects of cigarette smoke on killer cell activation in chronic obstructive pulmonary disease. PhD thesis, University of Nottingham.

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Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease involving both innate and adaptive immune responses. Abnormal numbers of inflammatory cells have been examined in COPD subjects, as well as the effects of cigarette smoking on immune cells and molecules. Killer cells, including CD8+ T cells, NKT-like cells and NK cells, are thought to play a role in the development of COPD through their cytotoxic functions. In this project, we report ex vivo, activation levels of these cell types in COPD patients, as well as effects induced by cigarette smoke extract in vitro.

PBMCs were collected from healthy non-smokers (HNS), current healthy smokers (HS), current smokers with COPD (cuS-COPD) and ex-smokers with COPD (exS-COPD). Activation levels of interest and CSE effects on them were analysed by flow cytometry.

Killer cells, including CD8+ T cells, NKT-like cells and NK cells, were significantly activated in current smokers with or without COPD compared to healthy non-smokers. Furthermore, KIR (CD158e1) expression was dramatically lower in smokers with or without COPD in comparison with healthy non-smokers. The cytotoxicity of CD8+ T cells from both current smokers and ex-smokers with COPD patients were significantly less than that in healthy volunteers. Also, in vitro, CSE markedly decreased IL-15 treated NK cell activation in current smokers with COPD compared to other three groups. The expression of granzyme B was also significantly inhibited on IL-15 stimulated NK cells when CSE was added.

We conclude systemic ex vivo killer cell activation is smoking rather than disease related. Cigrette smoking has immunosuppressive effects on killer cell activation and granzyme B expression in PBMCs from current smokers with COPD.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Fairclough, L.
Todd, I.
Keywords: Physiological effects of smoking, COPD, Killer cells, Ex vivo activation
Subjects: R Medicine > RC Internal medicine
W Medicine and related subjects (NLM Classification) > WF Respiratory system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 28241
Depositing User: Wang, Jia
Date Deposited: 05 Oct 2015 14:15
Last Modified: 13 Sep 2016 19:25
URI: http://eprints.nottingham.ac.uk/id/eprint/28241

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