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Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease.
- Source :
-
PloS one [PLoS One] 2016 Jan 25; Vol. 11 (1), pp. e0147232. Date of Electronic Publication: 2016 Jan 25 (Print Publication: 2016). - Publication Year :
- 2016
-
Abstract
- Background: CD8+ T cells (Cytotoxic T cells, Tc) are known to play a critical role in the pathogenesis of smoking related airway inflammation including chronic obstructive pulmonary disease (COPD). However, how cigarette smoke directly impacts systematic CD8+ T cell and regulatory T cell (Treg) subsets, especially by modulating muscarinic acetylcholine receptors (MRs), has yet to be well elucidated.<br />Methods: Circulating CD8+ Tc/Tregs in healthy nonsmokers (n = 15), healthy smokers (n = 15) and COPD patients (n = 18) were evaluated by flow cytometry after incubating with anti-CD3, anti-CD8, anti-CD25, anti-Foxp3 antibodies. Peripheral blood T cells (PBT cells) from healthy nonsmokers were cultured in the presence of cigarette smoke extract (CSE) alone or combined with MRs agonist/antagonist for 5 days. Proliferation and apoptosis were evaluated by flow cytometry using Ki-67/Annexin-V antibodies to measure the effects of CSE on the survival of CD8+ Tc/Tregs.<br />Results: While COPD patients have elevated circulating percentage of CD8+ T cells, healthy smokers have higher frequency of CD8+ Tregs. Elevated percentages of CD8+ T cells correlated inversely with declined FEV1 in COPD. CSE promoted the proliferation and inhibited the apoptosis of CD8+ T cells, while facilitated both the proliferation and apoptosis of CD8+ Tregs. Notably, the effects of CSE on CD8+ Tc/Tregs can be mostly simulated or attenuated by muscarine and atropine, the MR agonist and antagonist, respectively. However, neither muscarine nor atropine influenced the apoptosis of CD8+ Tregs.<br />Conclusion: The results imply that cigarette smoking likely facilitates a proinflammatory state in smokers, which is partially mediated by MR dysfunction. The MR antagonist may be a beneficial drug candidate for cigarette smoke-induced chronic airway inflammation.
- Subjects :
- Apoptosis drug effects
Atropine pharmacology
Cell Division drug effects
Female
Forced Expiratory Volume
Humans
Lymphocyte Activation drug effects
Lymphocyte Count
Male
Middle Aged
Muscarine pharmacology
Muscarinic Agonists pharmacology
Muscarinic Antagonists pharmacology
Inflammation etiology
Pulmonary Disease, Chronic Obstructive immunology
Receptors, Muscarinic physiology
Smoke adverse effects
Smoking immunology
T-Lymphocytes, Regulatory drug effects
Nicotiana
Tobacco Products
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26808506
- Full Text :
- https://doi.org/10.1371/journal.pone.0147232