The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells

Autor: Ming Li, Junhui Xiao, Chuanyin Xiong, Yuzhen Wei, Kunwu Yu, Qiutang Zeng
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Physiology
Apoptosis
Antigen-Antibody Complex
030204 cardiovascular system & hematology
Pharmacology
T-Lymphocytes
Regulatory
lcsh:Physiology
Mice
0302 clinical medicine
Medicine
lcsh:QD415-436
Myocytes
Cardiac
lcsh:QP1-981
Antibodies
Monoclonal
Interleukin-10
medicine.anatomical_structure
Cytokines
Immunotherapy
medicine.symptom
Ischaemia/reperfusion injury
Myocardial Reperfusion Injury
Spleen
Inflammation
Proinflammatory cytokine
lcsh:Biochemistry
Transforming Growth Factor beta1
03 medical and health sciences
In vivo
Splenocyte
Animals
Regulatory T-lymphocytes (Tregs)
business.industry
Myocardium
Hemodynamics
Interleukin-2 Receptor alpha Subunit
Th1 Cells
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Interleukin-2
Th17 Cells
Myocardial fibrosis
business
Reperfusion injury
Zdroj: Cellular Physiology and Biochemistry, Vol 44, Iss 5, Pp 1810-1827 (2017)
ISSN: 1421-9778
1015-8987
DOI: 10.1159/000485818
Popis: Background/Aims: Regulatory T cells (Tregs) can suppress immunologic damage in myocardial ischaemia/reperfusion injury (MIRI), however, the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate MIRI in mice. Methods: Myocardial I/R was surgically induced in male C57BL/6 mice, aged 8-10 weeks, that were randomly assigned to 1) sham group (Sham), 2) Phosphate Buffered Saline (PBS), 3) IL-2-anti-IL-2 Ab complex (IL-2C), or 4) sham group, 5) PBS, 6) IL-2C after MIRI, or 7) IL-2C, 8) IL-2C+anti-CD25 mAbs, or 9) IL-2C; 10) IL-2C+anti-TGF-β1 mAbs, 11) IL-2C+anti-IL-10 mAbs. The following parameters were measured at different time points: infarct area, myocardial apoptosis, splenocytes, the inhibitory function of Tregs, and presence of inflammatory factors. In addition, immunohistochemistry analysis was performed. Results: We observed that Tregs were activated in response to MIRI. IL-2C administered before MIRI induced Treg expansion in both spleen and heart, attenuated Th1 and Th17 cell numbers, improved myocardial function, and attenuated both infiltration of inflammatory cells and apoptosis after MIRI. Furthermore, IL-2C administration reduced expression of inflammatory cytokines in the heart and attenuated proliferation of splenic cells. Depletion of Tregs with anti-CD25 mAb abrogated the beneficial effects of IL-2C. However, IL-2C–mediated myocardial protection was not dependent on either IL-10 or TGF-β. In addition, IL-2C administration after MIRI did not reduce infarct area, but did improve myocardial function slightly and reduced myocardial fibrosis. Conclusion: Our results demonstrate that IL-2C–induced Treg expansion attenuates MIRI and improves myocardial recovery in vivo, suggesting that IL-2C is a promising therapeutic target for myocardial IRI.
Databáze: OpenAIRE
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