Levels of CD4CD25 T regulatory cells in bronchial mucosa and peripheral blood of chronic obstructive pulmonary disease indicate involvement of autoimmunity mechanisms

Abstract

Background: Many theories have been proposed to explain pathogenesis of COPD; however, remains unclear why the majority of smokers (~80 %) do not develop COPD, or only develop a mild disease. To explore if COPD has an autoimmune component, the role of T regulatory lymphocytes (Tregs) in the lung tissue of COPD patients is of a crucial importance.

Methods: Bronchial tissue biopsy samples were prospectively collected from 64 patients (39 COPD and 25 controls – 15 smokers and 10 non-smokers). The patients with COPD were subdivided into mild/moderate (GOLD stage I-II) and severe/very severe (GOLD stage III-IV) groups. Digital image analysis was performed to estimate densities of CD4⁺CD25⁺ cell infiltrates in double immunohistochemistry slides of the biopsy samples. Blood samples were collected from 42 patients (23 COPD and 19 controls) and tested for CD3⁺CD4⁺CD25^{+ bright} lymphocytes by flow cytometry.

Results: The number of intraepithelial CD4⁺CD25⁺ lymphocytes ^mm-2 epithelium was significantly lower in the severe/very severe COPD (GOLD III-IV) group as well as in the control non-smokers (NS) group (p<0,0001). Likewise, the absolute number of Treg (CD3⁺CD4⁺CD25^{+ bright}) cells in the peripheral blood samples was significantly different between the four groups (p=0.032). The lowest quantity of Treg cells was detected in the severe/very severe COPD and healthy non-smokers groups.

Conclusions: Our findings suggest that severe COPD is associated with lower levels of Tregs in the blood and bronchial mucosa, while higher Tregs levels in the smokers without COPD indicate potential protective effect of Tregs against developing COPD.

Keywords: COPD, autoimmunity, T- regulatory cell, bronchial biopsy, flow cytometry