The role of adaptive immunity in the development or progression of chronic obstructive pulmonary disease (COPD) remains undefined. Recently, the presence of autoantibodies and autoreactive T cells has been demonstrated in COPD patients. In addition, oligoclonal expansions of lung T cells have been observed in COPD patients, but the overlapping incidence of infections, tumors, and cigarette smoke exposure obscures the antigenic stimulus. We analyzed the TCR V␤ repertoire of CD4 and CD8 T cells purified from the lungs and spleens of mice chronically exposed to cigarette smoke. In a mouse model of COPD, we demonstrate that chronic cigarette smoke exposure causes oligoclonal expansions of T cells isolated from the lungs, but not spleens. TCR V␤ repertoire analyses revealed oligoclonal expansions predominantly occurred in lung CD8 T cells, with preferential usage of V␤7, V␤9, V␤13, and V␤14. Using nucleotide sequence analysis based on J␤ analyses, we demonstrate selection of CDR3 amino acid motifs, which strongly suggests Ag-driven oligoclonal T cell expansion. Analysis of the lung TCR V␤ repertoire of mice with cigarette smoke-induced emphysema, which had undergone smoking cessation for 6 mo, revealed that oligoclonal expansions persisted. This study formally demonstrates that chronic cigarette smoke exposure, alone, causes a persistent adaptive T cell immune response. These findings have important implications for therapeutic approaches in the treatment of COPD, and provide insight into potential mechanisms involved in disease pathogenesis.

Statins are widely used in patients with cardiovascular diseases. A considerable number of previous studies revealed that the intracellular signaling of transforming growth factor (TGF)-β1 mediated the development of cardiomyocyte hypertrophy and interstitial fibrosis. However, whether statins can ameliorate ventricular remodeling in post-myocardial infarction via the TGF-β1 signaling pathway remains to be rigorously tested. The left anterior descending artery was ligated to induce a rat model of myocardial infarction. The rat model of myocardial infarction was treated with simvastatin through gastric gavage (10, 20 or 40 mg kg−1·d−1). All rats were sacrificed on day 28 after the myocardial infarction operation. The results revealed that simvastatin significantly improved the hemodynamic indexes, left ventricular mass index, the myocardial tissue structure, the cardiomyocyte cross-sectional area and the collagen volume fraction, and also showed that the levels of TGF-β1, TGF-activated kinase (TAK)1 and drosophila mothers against decapentaplegic (Smad)3 were significantly reduced following treatment with simvastatin, while the levels of Smad7 in the simvastatin treatment groups were markedly increased. The results of the present study suggested that statins ameliorated ventricular remodeling in post-myocardial infarction rats via the TGF-β1 signaling pathway, which provided a novel explanation for the pleiotropic effects of statins that benefit the cardiovascular system.

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using tPSA value only (determining the best discriminating threshold for this specific dataset which resulted in 3.5 [ng/mL] then using MS data only) and finally by an algorithm of integration of tPSA and MS data. Different classification algorithms were tested, the best ones being Support Vector Machines (SVM). Integration was carried out by juxtaposition of PSA and MS values in a 0:1 scaled vector, and by assigning a coefficient of relative importance (weight) to the PSA and MS features; classification here was done recurring to decision tree classifier. All performances have been evaluated on the basis of a 1 0-fold crossvalidation, with 1 00 random realizations of the dataset.RESULTS: Sensitivity and Specificity (in %), with relative standard deviation, obtained by each method and valuated on a basis of 10-fold cross validation are shown in the table below: Method S~!ecificity

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