Biochemical and Biophysical Research Communications
Regular ArticleThe Role of CD8+ Th2 Lymphocytes in the Development of Smoking-Related Lung Damage
Abstract
There is increasing evidence for the existence of different subsets of CD8+ T lymphocytes in humans, according to their cytokine secretion profile. Resistance or susceptibility to infections and the outcome of some inflammatory processes may depend on the lymphokine profile which predominates. We show one consequence of the switching of a host CD8+ T cell response from the Th1 effector function to the Th2 pattern in relation to the exposure to a common toxicant and its pathogenetic implications. Chronic obstructive bronchitis is a pulmonary disease characterized by airway inflammation with predominance of CD8+ T lymphocytes, mucus hypersecretion, repeated airway infections, and decline in lung function. Though smoking-related, it affects only a portion of smokers. The results of this study, comparing the functional characteristics of CD8+ T cell clones from smokers with the disease, unaffected smokers and healthy individuals, indicate that the smokers who have a predominance of CD8+ T lymphocytes of the Th2 phenotype may be predisposed to develop more severe smoking-induced lung damage, with chronic airway inflammation, repeated infections and persistent airflow obstruction.
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Cited by (23)
Asthma and tobacco, an immunologic connection
2007, Medicina ClinicaThe smoking gun: Many conditions associated with tobacco exposure may be attributable to paradoxical compensatory autonomic responses to nicotine
2005, Medical HypothesesTobacco exposure is implicated in many illnesses such as cardiovascular disease and cancer, but the mechanisms underlying these associations are poorly understood. The mechanisms by which tobacco induces pro-sympathetic and pro-inflammatory changes also remain elusive. Some studies have attributed these changes to the direct effects of nicotine, but such findings run counter to the pro-vagal, anti-inflammatory nature of the nicotinic pathway. We hypothesize that the illnesses associated with smoking may be partly attributable to autonomic dysfunction, sympathetic bias, and T helper (Th)2 inflammation induced by a paradoxical compensatory response to intermittent nicotinic exposure. The confusion of interpreting the adrenergia and inflammation associated with nicotine as a primary response instead of a secondary compensation may be explained by the unusually rapid absorption, action, and serum elimination of nicotine. Given the fast action and clearance of nicotine, even heavy smokers spend large portions of the day and the entire night in nicotine withdrawal, at which time rebound sympathetic bias may manifest as a result of desensitization of nicotinic receptors. This may help reconcile why the features observed in smokers such as tachycardia, hypertension, inflammation, insomnia, and anxiety, which are perhaps mistakenly attributed to the direct action of nicotine, are identical to those seen during acute nicotine withdrawal after smoking cessation. On the other hand, delayed responses to cessation of smoking such as weight gain and increased heart rate variability are compatible with reduced sympathovagal ratio and resensitization of nicotinic receptors. Sympathetic bias and the associated Th2 inflammation underlie many systemic diseases. Tobacco-related cancers may be partly attributable to immunomodulatory properties of chronic nicotine exposure by dampening Th1 immunity and enabling tumoral evasion of immune surveillance. Other conditions associated with tobacco exposure may also operate through similar autonomic and immune dysfunctions. Therapeutic implications are discussed.
Tobacco and mucosal immunity: Inflammation or acquired immune deficiency
2004, Revue Francaise des LaboratoiresLes pathologies associées à l'usage du tabac sont nombreuses et pour certaines bien connues des médecins et du public, en particulier les cancers des interfaces épithéliales bronchiques, ORL et vésicales, mais d'autres pathologies à composante immunitaire lui sont aussi reliées. Les mécanismes physiopathologiques reliant exposition tabagique et pathologies sont paradoxalement encore mal connus, en particulier ceux concernant le système immunitaire et plus encore ceux mettant en jeu le système immunitaire muqueux. Cet article fait une revue des connaissances actuelles sur ce sujet sensible et de grande importance en Santé publique. Au niveau de l'immunité systémique, l'exposition tabagique induit un déficit immunitaire acquis, au moins partiel, qui peut favoriser le développement de phénomènes d'hypersensibilité et de pathologies auto-immunes. En ce qui concerne le système immunitaire muqueux, l'exposition à la fumée de tabac induit des anomalies acquises de l'immunité innée aussi bien que de l'immunité adaptative, auxquelles s'ajoutent des phénomènes inflammatoires locaux.
Tobacco usage induces many pathological disorders, most of them being well known from patients and medical people, particularly neoplasia of mucosal surfaces such as bronchi, ENT, and bladder, but other immune-mediated disorders can be attributed to tobacco smoke exposure. Physiopathological mechanisms remain paradoxically ill-known, particularly the effects on the systemic immune system, and moreover in the mucosal immune system. This paper reviews the knowledge on a major topic for public health. Considering the systemic immune system, tobacco smoke exposure induces an acquired immune deficiency which could induce hypersensitivity or autoimmune pathologies. Concerning the mucosal immune system, tobacco smoke exposure induces as well a local acquired immune deficiency of innate immunity and of adaptative immunity. Local inflammatory phenomena are often associated to produce clinical symptoms.
Induced sputum CD8<sup>+</sup> T-lymphocyte subpopulations in chronic obstructive pulmonary disease
2004, Respiratory MedicineBackground: Previous studies have shown that the inflammatory response to cigarette smoking differs between smokers who develop chronic obstructive pulmonary disease (COPD) and those who do not and that the CD8+ T-lymphocytes have been identified as a key player in this process. The aim of this study was to investigate further the role of CD8+ cells and their subtypes in sputum cells.
Methods: Sputum induction was performed in 36 COPD patients, 25 smokers without COPD and 10 non-smoking healthy controls. After stimulation of sputum lymphocytes with phorbol-myristate-acetate, we used double immunocytochemical methods to identify CD4+, CD8+ cells and CD8+ INFγ or IL4 cells (Tc1,Tc2).
Results: COPD patients had an increased number of CD8+ cells in sputum as compared with smokers without COPD (P=0.0001) and control subjects (P=0.001). CD8+-IL4 cells were reduced both in COPD and in smokers without COPD compared to controls (P=0.0001), while CD8+-IFNγ cells were significantly reduced only in COPD (P=0.001) as compared with controls. A significant (P=0.02) relationship between the CD8+-IL4/CD8+-IFNγ ratio and FEV1 (% pred) was found only in COPD patients.
Conclusion: These findings suggest that an imbalance both in T-lymphocyte subpopulation (CD4/CD8) and in CD8+ cell subsets (Tc1/Tc2) characterizes the inflammatory responses of smokers with established COPD.
The expression of lymphocyte surface antigens in bronchial biopsies, bronchoalveolar lavage cells and blood cells in healthy smoking and never-smoking men,60 years old
2000, Respiratory MedicineIn this study we investigated if smoking subjects with a normal or slightly decreased lung function differ in the lymphocyte pattern compared to never-smokers.
In a group of ‘healthy’ smokers (n=58) and never-smokers (n=34) 60 years old, we investigated the lymphocyte pattern in both BAL (n=30 and n=18 respectively), bronchial epithelium and lamina propria (n=14 andn =10 respectively) and blood.
We found that all subjects, despite smoking history, had a higher number of CD8+ cells per mm2in the epithelium compared to the lamina propria in the bronchial biopsies. In smokers, these CD8+ cells were significantly negatively correlated to FEV1(r=−0·56,P =0·04). In smokers, the number of CD8+ lymphocytes was higher and the T cell activation markers (CD57+ and CD28+) were lower in BAL, than in never-smokers. This last finding was also seen in blood for CD3+57+.
We conclude, that in ‘healthy’ smokers the lymphocyte patterns are different compared to never-smokers, to some extent in BAL. There is also a relation between lymphocytes in the bronchial mucosa and lung function. This has previously been shown in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis but not in asymptomatic smokers.
CD8<sup>+</sup> T cells in atonic disease
1998, Current Opinion in ImmunologyIn recent years there has been a tremendous expansion in our understanding about CD8+ T cells. We now know that, as for CD4+ T cells, they can be divided into subsets (Tc1 and Tc2) according to the cytokines they secrete. These subsets may differ in their capacity to kill and may even, in some cases, provide help for B cell antibody production or be involved in the induction of inflammatory responses. In addition, there is a host of cross-regulatory networks between different CD4+ and CD8+ subsets that control the magnitude and duration of immune responses. The observation that some antigens that are normally presented by MHC class II and seen by CD4+ T cells can be presented by MHC class I and stimulate CD8+ T cells increases the possibility for such interactions. During the next few years we can expect that our understanding of the biology of CD8+ T cells and their role in immunity will increase.
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To whom correspondence should be addressed: Dr. Sabrina Mattoli, Chair, Italian Foundation of Experimental medicine, Viale C. Battisti 5, 05100 Terni, Italy. Fax: (+39) 7 4458376.