Functional characterization of T cells in abdominal aortic aneurysms

Forester, Nerys; Cruickshank, Sheena M.; Scott, Daniel; Carding, Simon R.

doi:10.1111/j.1365-2567.2005.02157.x

Cited by 71 publications

(71 citation statements)

References 15 publications

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“…NPA-PCR/Vb-specific PCR amplification did not reveal any b-chain TCR transcripts (data not shown). These results are in agreement with those of other investigators (7,40,41) who reported the absence of CD45 + cells or T cells from nonaneurysmal aortic tissue. We (35) reported similar results with control epicardial arteries.…”

Section: T Cells Are Infiltrating Aaa Lesionssupporting

confidence: 83%

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: T Cells Are Infiltrating Aaa Lesionssupporting

confidence: 83%

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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“…We and others have reported that macrophage uptake occurs predominantly in the tunica adventitia in both humans and animal models (27,29,37,40,50,(52)(53)(54)(55)(56), in association with elastic lamellar tears. Initial adventitial recruitment is mediated by the potent chemotactic properties of MCP-1, followed by subsequent medial invasion (3,4,40,57,58).…”

Section: Discussionmentioning

confidence: 99%

An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice

Tieu¹,

Sun²,

LeJeune³

et al. 2009

J. Clin. Invest.

393

375

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Vascular inflammation contributes to cardiovascular diseases such as aortic aneurysm and dissection. However, the precise inflammatory pathways involved have not been clearly defined. We have shown here that subcutaneous infusion of Ang II, a vasopressor known to promote vascular inflammation, into older C57BL/6J mice induced aortic production of the proinflammatory cytokine IL-6 and the monocyte chemoattractant MCP-1. Production of these factors occurred predominantly in the tunica adventitia, along with macrophage recruitment, adventitial expansion, and development of thoracic and suprarenal aortic dissections. In contrast, a reduced incidence of dissections was observed after Ang II infusion into mice lacking either IL-6 or the MCP-1 receptor CCR2. Further analysis revealed that Ang II induced CCR2 + CD14 hi CD11b hi F4/80 -macrophage accumulation selectively in aortic dissections and not in aortas from Il6 -/-mice. Adoptive transfer of Ccr2 +/+ monocytes into Ccr2 -/-mice resulted in selective monocyte uptake into the ascending and suprarenal aorta in regions of enhanced ROS stress, with restoration of IL-6 secretion and increased incidence of dissection. In vitro, coculture of monocytes and aortic adventitial fibroblasts produced MCP-1-and IL-6-enriched conditioned medium that promoted differentiation of monocytes into macrophages, induced CD14 and CD11b upregulation, and induced MCP-1 and MMP-9 expression. These results suggest that leukocyte-fibroblast interactions in the aortic adventitia potentiate IL-6 production, inducing local monocyte recruitment and activation, thereby promoting MCP-1 secretion, vascular inflammation, ECM remodeling, and aortic destabilization.

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“…The predominant cell types within the infiltrate in AAA tissues are CD3 + T cells (more than 50%), including CD4 + T cells and CD8 + T cells [17]. CD8 + T cells have been found, dating as far back as 1999, in AAAs rather than normal aorta.…”

Section: Cd8 + T Cellsmentioning

confidence: 99%

“…Immunohistochemical staining and flow cytometry suggested that elevated numbers of CD3 + cells (include both CD3 + TCRαβ + and CD3 + TCRγδ + cells), localizing in aortic media and adventitia, were present in aneurysm patients [16,17], which may further led to the death of VSMCs [18]. With the evidence that oligoclonal αβ TCR+T cell populations expansion in aneurysmal lesions from AAA patients, AAA is considered as a specific antigen-driven T cell disease [19,20].…”

Section: T Cells In Aneurysmsmentioning

confidence: 99%

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T lymphocytes and aortic aneurysms

Cheng

2014

Sci. China Life Sci.

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Aortic aneurysms are common and life threatening problems with high rates of death. The initiation and progression of aneurysms are characterized by extensive extracellular matrix degradation and immune cells invasion within arterial wall. During the pathogenesis of all aneurysms, inflammation and immune cells play a significant role. Although T cells are abundant in aneurysm tissue, their functions in initiation and propagation of aneurysms remain unclear. This review summarizes the current state of knowledge of T lymphocytes on this disease and focuses on potential mechanisms of specific T cell responses.

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Functional characterization of T cells in abdominal aortic aneurysms

Cited by 71 publications

References 15 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

An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice

T lymphocytes and aortic aneurysms

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