Lymphocyte population and apoptosis in the lungs of smokers and their relation to emphysema

Abstract

Previously, it had been shown that T-lymphocytes are the predominant inflammatory cells found in the alveolar wall of smokers and their numbers correlated with the extent of emphysema. However, the phenotype of these cells was not defined. The aim of this study was to describe the different T-cell phenotypes and investigate the possible presence of apoptosis in the lung parenchyma of smokers.Samples from lungs were obtained at surgery from 15 patients who smoked and six who had never smoked. Samples were frozen and prepared for histological and immunocytochemical examination. Slides were stained for CD3+, CD4+, CD8+, γδ T-cells, CD56 natural killers ((NK) cells), and elastase (neutrophils). Anti-CD95 monoclonal antibodies andin situend-labelling techniques were used to detect Fas expression and apoptosis. Positive staining cells were expressed as cells·mm alveolar wall−1, percentage of total cells, and Fas/APO and apoptosis index. Emphysema was identified macroscopically, microscopically and reported as present or absent. All subjects had pulmonary function tests before surgery.Neutrophils were the predominant cell in the lung parenchyma of nonsmokers and smokers without emphysema. In smokers with emphysema, the CD3+ and CD8+ were the predominant cells (p<0.05) in the alveolar wall. γδ cells were increased in all smokers and no increased numbers of NK cells was found. The T-cell numbers·mm alveolar wall−1showed a bilinear relationship with the amount smoked increasing at an inflection point of 30 packs yr−1(R2=0.345; p<0.01). Apoptosis in smokers showed a bilinear relationship with the amount smoked increasing sharply in smokers with emphysema (R2=0.3613; p<0.009).It is concluded that the pathogenesis of emphysema might be mediated by T-lymphocytes, mainly CD8+ cytolytic T-cells, and that apoptosis might be one of the mechanisms of lung destruction leading to the development of emphysema. If this is the case, it could be speculated that T-cell inflammation is a response to antigenic stimuli originating in the lung and induced by cigarette smoking.

Oligoclonal CD4+T Cells in the Lungs of Patients with Severe Emphysema

“…Despite reports suggesting a more robust association between CD8 ϩ T cells and emphysema (9)(10)(11)(12), skewing of the TCR repertoire after culture was only present in the CD4 ϩ T-cell population. Other recent reports also highlight the importance of CD4 ϩ T cells in emphysema.…”

“…Although the etiology of this continued inflammation is unknown, studies have shown a correlation between the number of T cells present in the emphysematous lung and disease severity (7)(8)(9)(10)(11)(12). The stimulus responsible for T-cell recruitment into the lungs of these patients remains unknown.…”

Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

“…Emphysema, a key component of COPD, is characterized by destruction of the airways, leading to loss of elastic recoil and decline in lung function. Epithelial and endothelial cell apoptosis in the lung is critical to the development of emphysema (38)(39)(40). Mechanisms, such as oxidative stress, are well-appreciated for their role in apoptotic cell death following smoke exposure (38,41).…”

Chronic Obstructive Pulmonary Disease: Evidence for an Autoimmune Component

“…Although such observations implicate T cell responses in COPD pathogenesis, the precise role of particular T cell subsets in disease progression remains ill defined. A major consequence of effector CD8 + T cell function is the apoptosis of target cells through a FasL or perforin/granzyme dependent mechanism and a number of groups have demonstrated a correlation between the levels of T cell infiltration and apoptosis related tissue destruction in the emphysematous lung (35,36). Although the nature of the CD4 + T cell response in the lungs of COPD patients is less well characterized it is accepted that in order for most classes of CD8 + T cell responses to be mounted effectively, CD4 + T cell 'help' is required.…”