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Clin Exp Immunol. 2009 Mar;155(3):466-75. doi: 10.1111/j.1365-2249.2008.03835.x.

T cell senescence and contraction of T cell repertoire diversity in patients with chronic obstructive pulmonary disease.

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Department of Pulmonary Medicine, Medical University of Vienna, Vienna, Austria.


Pathogenetic mechanisms leading to chronic obstructive pulmonary disease (COPD) remain poorly understood. Because clonogenic T cells (CD4(+)CD28(null)) were shown to be increased in autoimmune diseases we hypothesized that CD4(+)CD28(null) T cells play a role in COPD. Here we describe that enhanced presence of CD4(+)CD28(null) cells is associated with impaired lung function. Sixty-four patients and controls were included. T cell phenotype was analysed using flow cytometry. Enzyme-linked immunosorbent assays were utilized to determine cytokines. Statistical evaluations were performed using non-parametric group comparisons and correlations. A logistic regression model was used to determine predictive values of CD4(+)CD28(null) in the diagnosis of COPD. Populations of CD4(+) T cells lacking surface co-stimulatory CD28 were enlarged significantly in evaluated patients when compared with controls. Natural killer (NK)-like T cell receptors (CD94, 158) and intracellular perforin, granzyme B were increased in CD4(+)CD28(null) cells. Cytokine production after triggering of peripheral blood mononuclear cells (PBMCs) was elevated in patients at early disease stages. Receiver operating characteristic curve plotting revealed that presence of CD4(+)CD28(null) T cells has a diagnostic value. These CD4(+)CD28(null) T cells show increased expression of NK-like T cell receptors (CD94, 158) and intracellular perforin and granzyme B. Furthermore, triggering of PBMCs obtained from patients with mild COPD led to increased interferon-gamma and tumour necrosis factor-alpha production in vitro compared with controls. Our finding of increased CD4(+)CD28(null) T cells in COPD indicates that chronic antigen exposure, e.g. through contents of smoke, leads to loss of CD28 and up-regulation of NK cell receptors expression on T cells in susceptible patients.

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