Deficient CD4
            <sup>+</sup>
            CD25
            <sup>+</sup>
            T Regulatory Cell Function in Patients With Abdominal Aortic Aneurysms

Yin, Ming; Zhang, Jian; Wang, Yong; Wang, Shaoye; Böckler, Dittmar; Duan, Zhi-quan; Xin, Shijie

doi:10.1161/atvbaha.109.200303

Cited by 88 publications

(71 citation statements)

References 24 publications

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“…gd TCR + T cells also were clonally expanded in AAA lesions, and this includes the various forms of gd TCR + T cells previously reported (9,44). The frequency and the suppressor activity of CD4 + CD25 + FOXP3 + T cells in the pe- ripheral blood of patients with AAA were significantly lower versus with those in patients with abdominal aortic atherosclerotic occlusive disease or healthy donors (45). These results demonstrate impaired immunoregulation in AAA, which may play a role in the pathogenesis of the disease.…”

Section: Discussionmentioning

confidence: 73%

Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

White

Lin

et al. 2014

The Journal of Immunology

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Abdominal aortic aneurysm (AAA) is a common disease with often life-threatening consequences. This vascular disorder is responsible for 1–2% of all deaths in men aged 65 years or older. Autoimmunity may be responsible for the pathogenesis of AAA. Although it is well documented that infiltrating T cells are essentially always present in AAA lesions, little is known about their role in the initiation and/or progression of the disease. To determine whether T cells infiltrating AAA lesions contain clonally expanded populations of T cells, we amplified β-chain TCR transcripts by the nonpalindromic adaptor–PCR/Vβ-specific PCR and/or Vβ-specific PCR, followed by cloning and sequencing. We report in this article that aortic abdominal aneurysmal lesions from 8 of 10 patients with AAA contained oligoclonal populations of T cells. Multiple identical copies of β-chain TCR transcripts were identified in these patients. These clonal expansions are statistically significant. These results demonstrate that αβ TCR+ T lymphocytes infiltrating aneurysmal lesions of patients with AAA have undergone proliferation and clonal expansion in vivo at the site of the aneurysmal lesion, in response to unidentified self- or nonself Ags. This evidence supports the hypothesis that AAA is a specific Ag–driven T cell disease.

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Section: Discussionmentioning

confidence: 73%

Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

White

Lin

et al. 2014

The Journal of Immunology

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“…19,[25][26][27] Similarly, a recent clinical study has suggested that such an imbalance may also be involved in the pathogenesis of AAA and that expansion of Tregs could be a promising strategy to prevent AAA. 16 However, obstacles still remain for clinical applications such as cell-based therapy involving transfer of ex vivo expanded Tregs because of difficulties in separating pure Tregs and maintaining them stable after expansion on antigenic stimulation. Although other therapeutic approaches should be considered, no study has uncovered the effects of endogenous 17 Our recent study has shown that IL-2 complex treatment efficiently shifts the Treg/Teff balance toward Tregs, associated with its highly activated status, without affecting the Th1/Th2 balance.…”

Section: Discussionmentioning

confidence: 99%

Foxp3 ⁺ Regulatory T Cells Play a Protective Role in Angiotensin II–Induced Aortic Aneurysm Formation in Mice

et al. 2015

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Although regulatory T cells (Tregs) have been shown to play a protective role in abdominal aortic aneurysm (AAA) formation, it remains unclear whether expansion of endogenous Foxp3 + Tregs prevents AAA. In the current study, we determined the effects of endogenous Foxp3 + Treg expansion or depletion in an experimental model of AAA. We continuously infused 12-week-old apolipoprotein E–deficient mice fed a high-cholesterol diet with angiotensin II (n=60) or normal saline (n=12) by implanting osmotic mini-pumps and evaluated AAA formation at 16 weeks. The angiotensin II–infused mice received interleukin-2/anti–interleukin-2 monoclonal antibody complex (interleukin-2 complex; n=31) or PBS (n=29). Eighty-one percent of angiotensin II–infused mice developed AAA, with 42% mortality possibly because of aneurysm rupture. Interleukin-2 complex treatment systemically increased the number of Foxp3 + Tregs and significantly decreased the incidence (52%) and mortality (17%) of AAA. Immunohistochemical analysis showed reduced accumulation of macrophages and increased numbers of Foxp3 + Tregs in aneurysmal tissues, suggesting that expansion of Tregs may suppress local inflammation in the vessel wall and provide protection against AAA formation. Furthermore, genetic depletion of Foxp3 + Tregs led to a significant increase in the mortality of AAA, suggesting the protective role of Foxp3 + Tregs against AAA. Our findings suggest that Foxp3 + Tregs may play a protective role in AAA formation and that promotion of an endogenous regulatory immune response may be a potentially valuable therapeutic approach for preventing AAA.

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“…Tregs have been reported to exert beneficial effects on the progression of numerous diseases (9,10), including atherlerosclerosis (11), abdominal aortic aneurysms (12) and inflammatory bowel disease (13). However, the role of Tregs in the development of PAH remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice

Chu

XiangLi

2014

Molecular Medicine Reports

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Abstract. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by the complex proliferation of the pulmonary vascular endothelium and progressive pulmonary vascular remodeling. CD4 + CD25+ regulatory T cells (Tregs) have been the focus of numerous studies into PAH. The present study aimed to investigate the role and mechanisms of Tregs in hypoxia-induced PAH. A total of 60 male mice were divided at random into three groups: Normoxia group, hypoxia control group and Tregs group. Measurements were obtained of the right ventricle systolic pressure (RVSP) and the Fulton's index; in addition, the mRNA and protein expression of pro-inflammatory cytokines including monocyte chemotactic protein 1 (MCP-1), interleukin (IL)-1β and IL-6, as well as the anti-inflammatory cytokine IL-10 in the lungs were determined by reverse transcription quantitative polymerase chain reaction and western blot analysis in vivo. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic condition with or without Tregs for 48 h, and the proliferation rate and cell cycle of HPASMCs were determined. In addition, the protein levels of phosphorylated (p)-Akt and p-extracellular signal-regulated kinase (ERK) were measured in HPASMCs in vitro. The results showed that Treg treatment significantly reduced the increased the hypoxia-induced RVSP and Fulton's index, decreased pro-inflammatory cytokine expression as well as enhanced IL-10 levels in vivo. Furthermore, Treg treatment significantly reduced HPASMCs proliferation and the expression of cyclin D1, cyclin-dependent kinase (CDK)4, p-Akt and p-ERK, as well as increased p27 expression in vitro.In conclusion, the results of the present study indicated that Tregs protected against hypoxia-induced PAH in mice; the mechanisms of which may proceed via the suppression of the inflammatory response, as Tregs were found to enhance anti-inflammatory cytokine levels, inhibit HPASMCs proliferation and regulate the cell cycle. These results therefore indicated that Tregs may be a potential novel target for the treatment of PAH.

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Deficient CD4 ⁺ CD25 ⁺ T Regulatory Cell Function in Patients With Abdominal Aortic Aneurysms

Cited by 88 publications

References 24 publications

Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

Foxp3 ⁺ Regulatory T Cells Play a Protective Role in Angiotensin II–Induced Aortic Aneurysm Formation in Mice

Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice

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Deficient CD4 + CD25 + T Regulatory Cell Function in Patients With Abdominal Aortic Aneurysms

Cited by 88 publications

References 24 publications

Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

Foxp3 + Regulatory T Cells Play a Protective Role in Angiotensin II–Induced Aortic Aneurysm Formation in Mice

Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice

Contact Info

Product

Resources

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Deficient CD4 ⁺ CD25 ⁺ T Regulatory Cell Function in Patients With Abdominal Aortic Aneurysms

Foxp3 ⁺ Regulatory T Cells Play a Protective Role in Angiotensin II–Induced Aortic Aneurysm Formation in Mice