[Muscarinic cholinergic receptor antagonists enhanced the expression of CD(8)(+)CD(25)(+)Foxp(3)(+) regulatory T cells in stable COPD patients].
OBJECTIVE
to investigate the levels of peripheral CD(8)(+)CD(25)(+)Foxp(3)(+) regulatory T cells (CD(8)(+)CD(25)(+)Treg) in stable chronic obstructive pulmonary disease (COPD) patients, and the effect of muscarinic cholinergic receptor antagonist, tiotropium bromide, on the expression of CD(8)(+)CD(25)(+)Treg.


METHODS
from Oct. 2007 to Mar. 2008, 23 patients with stable moderate to severe COPD received tiotropium bromide inhalation (18 microg daily) for 3 months. Before and after the use of tiotropium bromide, lung function was performed and peripheral vein blood samples were collected from the patient. Lymphocytes were isolated by three-color labeled monoclonal antibodies flow cytometry to detect the quantity and percentage of CD(8)(+)T cell, CD(8)(+)CD(25)(+) T cell, CD(8)(+)CD(25)(+)Treg, CD(4)(+)T cell, CD(4)(+)CD(25)(+) T cell and CD(4)(+)CD(25)(+)Treg, respectively. Paired t test was used for comparison between data before and after treatment.


RESULTS
in patients with stable COPD, after tiotropium bromide treatment, the percentage of CD(4)(+) T cells was increased from (28 +/- 10)% to (36 +/- 6)%, and the difference was significant (t = 3.20, P < 0.01). CD(4)(+)CD(25)(+) was decreased from (10 +/- 7)% to (4 +/- 3)% (t = 3.78, P < 0.01), and CD(8)(+)CD(25)(+)Treg was increased from (8 +/- 8)% to (21 +/- 21)% (t = 2.72, P < 0.05). At baseline, CD(8)(+) cells, CD(8)(+)CD(25)(+) cells and CD(4)(+)CD(25)(+)Treg were detectable in the peripheral blood, but no significant changes were observed after treatment. After treatment with tiotropium bromide, the lung function was markedly improved; FEV(1), FEV(1)/Pre%, and FEV(1)/FVC were increased from (1.0 +/- 0.3) L, (35 +/- 10)% and (41 +/- 8)% to (1.1 +/- 0.3) L, (40 +/- 11)% and (45 +/- 11)%, respectively (t = 2.65, 2.56 and 2.37, respectively, all P < 0.05). By linear correlation analysis, the quantity of changes of CD(4)(+) T cells and CD(4)(+)CD(25)(+) T cells were negatively correlated with the rate of change in CD(8)(+)CD(25)(+)Treg (r = -0.61, P < 0.05 and r = -0.72, P < 0.01, respectively).


CONCLUSIONS
in the peripheral blood of patients with stable COPD, there was expression of CD(8)(+)CD(25)(+)Treg and CD(4)(+)CD(25)(+)Treg. The muscarinic receptor antagonist tiotropium bromide, promoted the amplification of CD(4)(+), inhibited the expression of CD(25)(+), and enhanced the expression of CD(8)(+)Treg, suggesting that muscarinic receptor antagonist tiotropium bromide may possess immunomodulation function.
Zhang
Jian-Chu
JC
Department of Respiratory Deseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Wang
Pei
P
Xiong
Xian-Zhi
XZ
Deng
Li
L
Xin
Jian-Bao
JB
Ma
Wan-Li
WL
Shi
Huan-Zhong
HZ
D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D000069447:Tiotropium Bromide
D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide