Differential effects of smoking and COPD upon circulating myeloid derived suppressor cells

Background: Chronic obstructive pulmonary disease (COPD) is characterized by an enhanced and persistent innate and acquired immune response to tobacco smoking. Myeloid-derived suppressor cells (MDSCs) modulate T-cell responses by down-modulating the T cell receptor zeta chain (TCR zeta) through the catabolism of L-arginine. The effects of smoking on MDSCs and their potential participation in COPD immunopathogenesis have not been explored so far. Methods: To investigate it, we compared the level of circulating Lineage-/HLA-DR-/CD33+/CD11b+MDSCs, the serum concentration of arginase I (ARG I) and the expression of peripheral T-cell receptor zeta chain (TCR zeta) in never smokers, smokers with normal spirometry and COPD patients. Flow cytometry was used to quantify circulating MDSCs and TCR zeta expression. Serum ARG I levels were determined by ELISA. Results: The main findings of this study were that: (1) current smoking upregulates and activates circulating MDSCs both in smoker controls and COPD patients; and, (2) at variance with the smokers with normal spirometry, in patients with COPD this effect persists after quitting smoking and is accompanied by a significant and specific down-regulation of the TCR zeta chain expression in circulating T lymphocytes. Conclusion: Smoking modulates circulating MDSCs. Their regulation appears altered in patients with COPD. (C) 2013 Elsevier Ltd. All rights reserved.