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Functional profile of activated dendritic cells in unstable atherosclerotic plaque

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Abstract

Background

Unstable atherosclerotic plaque typically contains an infiltrate of activated macrophages and activated T cells. This study established a functional profile of plaque-residing dendritic cells (DC) to examine whether they can function as Ag-presenting cells to facilitate in situ T-cell activation.

Methods

Carotid artery plaque tissues were collected from 19 asymptomatic and 38 symptomatic patients undergoing endarterectomy. Matched samples of normal coronary artery wall, stable nonruptured plaque, and eroded unstable plaque were harvested from patients with fatal myocardial infarction. Quantitative PCR and immunohistochemistry were used to analyze the tissues for markers of DC activation (CD83, CD86, CCL19,CCL21) and correlate them with T-cell activation (IFN-γ,TNF-α).

Results

Carotid artery plaques from patients with ischemic symptoms compared to asymptomatic patients were characterized by the presence of high amount of T-cells (P < 0.01) and tissue production of high levels of the T-cell cytokines IFN-γ (P = 0.001) and TNF-α (P = 0.006). Plaque tissues from patients with ischemic complications contained elevated levels of CD83 (P < 0.001), a marker of DC activation, and the DC chemokines CCL19 (P = 0.001) and CCL21 (P < 0.02).

Unstable coronary artery plaques were similarly correlated compared to carotid plaques from symptomatic patients with the accumulation of T cells (P = 0.001) and the production of T cell chemokines IFN-γ (P = 0.001) and TNF-α (P = 0.002).

Immunohistochemistry confirmed the presence of CD83+ DC in the shoulder region of unstable plaques, where they produced the T cell-attracting chemokines CCL19 and CCL21. Mapping of activated DC demonstrated close contact between mature DC and T cells expressing the activation marker CD40 ligand (CD40L).

Conclusion

Activated and fully mature DC are represented in the inflammatory infiltrate characteristic for unstable carotid and coronary atheroma. Such DC produce chemokines, and thus can regulate the cell traffic into the lesion. Through the expression of the costimulatory ligand CD86, plaque-residing DC can augment T-cell stimulation and provide optimal stimulation conditions for T lymphocytes, resembling the microenvironment in organized lymphoid tissues.

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Authors and Affiliations

  1. Dept. of Cardiology, Internal Medical Clinic III University of Heidelberg, INF 410, 69120, Heidelberg, Germany

    C. Erbel MD

  2. Dept. of Medicine, Lowance Center for Human Immunology Emory School of Medicine, Atlanta, (GA), USA

    K. Sato MD, J. J. Goronzy MD & C. M. Weyand MD

  3. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, (MN), USA

    S. L. Kopecky MD & R. L. Frye MD

  4. Division of Neurosurgery, Mayo Clinic, Rochester, (MN), USA

    F. B. Meyer MD

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  1. C. Erbel MD
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  2. K. Sato MD
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  3. F. B. Meyer MD
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  4. S. L. Kopecky MD
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  5. R. L. Frye MD
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  6. J. J. Goronzy MD
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  7. C. M. Weyand MD
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Correspondence to C. Erbel MD.

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Erbel, C., Sato, K., Meyer, F.B. et al. Functional profile of activated dendritic cells in unstable atherosclerotic plaque. Basic Res Cardiol 102, 123–132 (2007). https://doi.org/10.1007/s00395-006-0636-x

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  • DOI: https://doi.org/10.1007/s00395-006-0636-x

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