open access

Vol 87, No 3 (2019)
ORIGINAL PAPERS
Published online: 2019-06-28
Submitted: 2019-01-07
Accepted: 2019-04-24
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Levels of CD4+ CD25+ T regulatory cells in bronchial mucosa and peripheral blood of chronic obstructive pulmonary disease indicate involvement of autoimmunity mechanisms

Virginija Sileikiene, Aida Laurinaviciene, Daiva Lesciute-Krilaviciene, Laimute Jurgauskiene, Radvile Malickaite, Arvydas Laurinavicius
DOI: 10.5603/ARM.2019.0023
·
Pubmed: 31282557
·
Adv Respir Med 2019;87(3):159-166.

open access

Vol 87, No 3 (2019)
ORIGINAL PAPERS
Published online: 2019-06-28
Submitted: 2019-01-07
Accepted: 2019-04-24

Abstract

Introduction: 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 crucial importance.
Material and 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.
Conclusion: 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.

Abstract

Introduction: 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 crucial importance.
Material and 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.
Conclusion: 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.

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Keywords

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

About this article
Title

Levels of CD4+ CD25+ T regulatory cells in bronchial mucosa and peripheral blood of chronic obstructive pulmonary disease indicate involvement of autoimmunity mechanisms

Journal

Advances in Respiratory Medicine

Issue

Vol 87, No 3 (2019)

Pages

159-166

Published online

2019-06-28

DOI

10.5603/ARM.2019.0023

Pubmed

31282557

Bibliographic record

Adv Respir Med 2019;87(3):159-166.

Keywords

COPD
autoimmunity
T- regulatory cell
bronchial biopsy
flow cytometry

Authors

Virginija Sileikiene
Aida Laurinaviciene
Daiva Lesciute-Krilaviciene
Laimute Jurgauskiene
Radvile Malickaite
Arvydas Laurinavicius

References (25)
  1. Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004; 350(26): 2645–2653.
  2. Cosio MG, Saetta M. Evasion of COPD in smokers: at what price? Eur Respir J. 2012; 39(6): 1298–1303.
  3. Plumb J, Smyth LJC, Adams HR, et al. Increased T-regulatory cells within lymphocyte follicles in moderate COPD. Eur Respir J. 2009; 34(1): 89–94.
  4. Lapperre TS, Postma DS, Gosman MME, et al. Relation between duration of smoking cessation and bronchial inflammation in COPD. Thorax. 2006; 61(2): 115–121.
  5. Roos-Engstrand E, Ekstrand-Hammarström B, Pourazar J, et al. Influence of smoking cessation on airway T lymphocyte subsets in COPD. COPD. 2009; 6(2): 112–120.
  6. Plumb J, Smyth LJC, Singh D. Role of regulatory T-cells in chronic obstructive pulmonary disease. AoRM. 2009.
  7. Cederbom L, Hall H, Ivars F. CD4+CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur J Immunol. 2000; 30(6): 1538–1543.
  8. Smyth LJC, Starkey C, Vestbo J, et al. CD4-regulatory cells in COPD patients. Chest. 2007; 132(1): 156–163.
  9. Barceló B, Pons J, Ferrer JM, et al. Phenotypic characterisation of T-lymphocytes in COPD: abnormal CD4+CD25+ regulatory T-lymphocyte response to tobacco smoking. Eur Respir J. 2008; 31(3): 555–562.
  10. Lee SH, Goswami S, Grudo A, et al. Antielastin autoimmunity in tobacco smoking-induced emphysema. Nat Med. 2007; 13(5): 567–569.
  11. Isajevs S, Taivans I, Strazda G, et al. Decreased FOXP3 expression in small airways of smokers with COPD. Eur Respir J. 2009; 33(1): 61–67.
  12. Barceló B, Pons J, Fuster A, et al. Intracellular cytokine profile of T lymphocytes in patients with chronic obstructive pulmonary disease. Clin Exp Immunol. 2006; 145(3): 474–479.
  13. Saetta M, Baraldo S, Corbino L, et al. CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999; 160(2): 711–717.
  14. Kheradmand F, Shan M, Xu C, et al. Autoimmunity in chronic obstructive pulmonary disease: clinical and experimental evidence. Expert Rev Clin Immunol. 2012; 8(3): 285–292.
  15. Domagała-Kulawik J, Hoser G, Dąbrowska M, et al. CD4+/CD25+ cells in systemic inflammation in COPD. Scand J Immunol. 2011; 73(1): 59–65.
  16. Li XN, Pan X, Qiu D. Imbalances of Th17 and Treg cells and their respective cytokines in COPD patients by disease stage. Int J Clin Exp Med. 2014; 7(12): 5324–5329.
  17. Caramori G, Ruggeri P, Di Stefano A, et al. Autoimmunity and COPD: Clinical Implications. Chest. 2018; 153(6): 1424–1431.
  18. Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet. 2011; 378(9795): 1015–1026.
  19. D'Alessio FR, Tsushima K, Aggarwal NR, et al. CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury. J Clin Invest. 2009; 119(10): 2898–2913.
  20. Chiappori A, Folli C, Balbi F, et al. CD4(+)CD25(high)CD127(-) regulatory T-cells in COPD: smoke and drugs effect. World Allergy Organ J. 2016; 9: 5.
  21. Hou J, Sun Y, Hao Yu, et al. Imbalance between subpopulations of regulatory T cells in COPD. Thorax. 2013; 68(12): 1131–1139.
  22. Cappello F, Caramori G, Campanella C, et al. Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis. PLoS One. 2011; 6(11): e28200.
  23. Pridgeon C, Bugeon L, Donnelly L, et al. Regulation of IL-17 in chronic inflammation in the human lung. Clin Sci (Lond). 2011; 120(12): 515–524.
  24. Sales DS, Ito JT, Zanchetta IA, et al. Regulatory T-Cell Distribution within Lung Compartments in COPD. COPD. 2017; 14(5): 533–542.
  25. Caramori G, Casolari P, Barczyk A, et al. COPD immunopathology. Semin Immunopathol. 2016; 38(4): 497–515.

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