• W J Zhuang, Y Xie, J L Gu, and S Y Wei.
• Department of General Medicine, Tianjin Occupational Diseases Precaution and Therapeutic Hospital, Tianjin 300070, China.
• Zhonghua Jie He He Hu Xi Za Zhi. 2018 Dec 12; 41 (12): 959-966.

AbstractObjective: To study the role and mechanism of CD(4)(+) CD(25)(+) FoxP3(+) regulatory T cells (Tregs) in the pathophysiological process of indirect acute lung injury (iALI) in mice. Methods: The iALI model was successfully induced by shock/cecal ligation and puncture method. Sham (n=8), cecal ligation and puncture (CLP, n=10), and hemorrhage (Hem, n=12) groups were established as controls. Two experimental groups were established: CLP+Hem (n=15) without Tregs adoptive transfer (AT), and CLP+Hem with Tregs adoptive transfer (CLP+Hem+AT, n=14). The number of Tregs, subsets of lymphocytes, neutrophil activity, apoptosis, cytokine levels and histopathological changes were measured in the lung tissue of each group. The protein exudation and the expression of IL-10 in bronchoalveolar lavage fluid (BALF) were also detected. After in vitro cell co-culture, the proliferation of activated T cells and the expression of IL-10, INF-γ and iNOS protein were detected. Results: The percentage and the absolute cell number of CD(4)(+) CD(25)(+) FoxP3(+) Tregs in lung tissue of iALI mice were (2.530±0.086)%, and (1.441±0.090)×10(4)/ml, respectively, which were significantly higher than the control groups (P<0.05). Adoptive transfer of Tregs could significantly decrease CD3-positive T lymphocytes, myeloperoxidase (MPO) activity, caspase-3 activity in lung tissue as well as protein leakage in BALF (P<0.05). Meanwhile interleukin-10 (IL-10) levels in lung tissue and BALF were up-regulated from (121.4±43.76) pg/ml to (201.0±61.96) pg/ml (t=2.776, P<0.05) and (206.2±90.88) pg/ml to (339.4±109.5) pg/ml (t=2.477, P<0.05), respectively. Histopathology was also significantly improved. The proliferation of activated T lymphocytes in the adoptive transfer Treg (AT-Treg) group (n=5) was significantly lower than that in the natural regulatory T cell (N-Treg) group (n=5, t=7.485, P<0.01) and the negative control group (n=5, t=16.66, P<0.01). However, iNOS enzyme inhibitor L-NMMA could significantly reduce the T cell proliferation (P<0.05). Conclusion: CD(4)(+)CD(25)(+)FoxP3(+) Tregs could reduce inflammatory reaction in mice with iALI, and the iNOS signaling pathway may be involved in this process.

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