Decreased Regulatory T Cells in Vulnerable Atherosclerotic Lesions: Imbalance between Pro‐ and Anti‐Inflammatory Cells in Atherosclerosis

Abstract

Atherosclerosis is a chronic inflammatory disease of the arterial wall in which presentation of autoantigens by dendritic cells (DCs) leads to the activation of T cells. Anti-inflammatory cells like Tregs counterbalance inflammation in atherogenesis. In our study, human carotid plaque specimens were classified as stable (14) and unstable (15) according to established morphological criteria. Vessel specimens (n = 12) without any signs of atherosclerosis were used as controls. Immunohistochemical staining was performed to detect different types of DCs (S100, fascin, CD83, CD209, CD304, and CD123), proinflammatory T cells (CD3, CD4, CD8, and CD161), and anti-inflammatory Tregs (FoxP3). The following results were observed: in unstable lesions, significantly higher numbers of proinflammatory cells like DCs, T helper cells, cytotoxic T cells, and natural killer cells were detected compared to stable plaques. Additionally, there was a significantly higher expression of HLA-DR and more T cell activation (CD25, CD69) in unstable lesions. On the contrary, unstable lesions contained significantly lower numbers of Tregs. Furthermore, a significant inverse correlation between myeloid DCs and Tregs was shown. These data suggest an increased inflammatory state in vulnerable plaques resulting from an imbalance of the frequency of local pro- and anti-inflammatory immune cells.

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“…However, the number and function of these cells decreases both in plaques and in circulation as disease progresses, consistent with a breakdown in tolerance and the appearance of proinflammatory T cells (9)(10)(11)(12). The Li study confirmed this decline in circulating Treg numbers alongside the expression levels of TGF-β and FoxP3 mRNA in PBMC from atherosclerotic patients, reflected in the serum by decreased TGF-β protein levels when measured by ELISA.…”

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“…T cells were then continuously present in later stages (fibroathermomas) of coronary arteries. Many studies have also detected T cells within carotid plaques (Kleindienst et al, ; Palma et al, ; de Boer et al, ; Chen et al, ; Erbel et al, ; Dietel et al, ; Rohm et al, ). Plaques of otherwise similar status in older patients contain higher levels of infiltrating T cells (Najib et al, ).…”

ATVB Distinguished Scientist Award

“…DC in human atherosclerotic lesions express CD83 and the content of CD83 + mature DC increased significantly in unstable plaques as compared to stable ones. 70, 71 CD83 regulates B cell activation and germinal center responses 72 as well as CD4 + T cell development. 73, 74 Although largely expressed by activated APCs, the costimulatory function of CD83 seems to be dispensable for murine T cell activation whilst CD83-stimulated human monocytes suppressed T cell responses.…”