Hypercholesterolemia Induces a Mast Cell–CD4+ T Cell Interaction in Atherosclerosis

Abstract

Mast cells (MCs) are potent innate immune cells that aggravate atherosclerosis through the release of proinflammatory mediators inside atherosclerotic plaques. Similarly, CD4 + T cells are constituents of the adaptive immune response and accumulate within the plaques following lipid-specific activation by APCs. Recently it has been proposed that these two cell types can interact in a direct manner. However, no indication of such an interaction has been investigated in the context of atherosclerosis. In our study, we aimed to examine whether MCs can act as APCs in atherosclerosis, thereby modulating CD4 + T cell responses. We observed that MCs increased their MHC class II expression under hyperlipidemic conditions both in vivo and in vitro. Furthermore, we showed that MCs can present Ags in vivo via MHC class II molecules. Serum from high-fat diet-fed mice also enhanced the expression of the costimulatory molecule CD86 on cultured MCs, whereas OVA peptide-loaded MCs increased OT-II CD4 + T cell proliferation in vitro. The aortic CD4 + and T H1 cell content of atherosclerotic mice that lack MCs was reduced as compared with their wild-type counterparts. Importantly, we identified MCs that express HLA-DR in advanced human atheromata, indicating that these cells are capable of Ag presentation within human atherosclerotic plaques. Therefore, in this artice, we show that MCs may directly modulate adaptive immunity by acting as APCs in atherosclerosis.

Mast Cells, Angiogenesis and Lymphangiogenesis in Human Gastric Cancer

“…Figure 2B and elegant studies by Ammendola and collaborators have demonstrated that the density of mast cells is markedly increased in metastatic draining lymph nodes of gastric cancer patients [168,219]. This suggests that mast cells can migrate to tumour draining lymph nodes (TDLNs) where they can act as non-professional antigen presenting cells [234,235]. The mast cell contribution to the evolving microenvironment of TDLNs remains poorly understood.…”

Immune-Mediated Inflammation in Vulnerable Atherosclerotic Plaques

“…In ApoE −/− mice on high triglyceride and cholesterol “Western-type” diet and restraint stress, mast cell activation correlated with plaque destabilization [69]. Mast cells of advanced human atherosclerotic lesions express Human Leucocyte Antigen (HLA)-DR, suggesting modulation of adaptive immunity by acting as antigen presenting cells [70]. Activated human mast cells release tryptase, chymase, carboxypeptidase A3, cathepsin G, and granzyme B.…”

Resveratrol Ameliorates Atherosclerosis Induced by High-fat Diet and LPS in ApoE-/- Mice and Inhibits the Activation of CD4+ T Cells

“…RES inhibited the proliferation and activation of CD4 + T cells both in atherosclerotic mice and in cultured splenic CD4 + T cells in vitro, which remained us that RES ameliorated AS by inhibiting the proliferation and activation of CD4 + T cells. CD4 + T cells are constituents of the adaptive immune response [46]. Activated CD4 + T cells secrete proinflammatory cytokines and inflammation mediated by activated CD4 + T cells plays an important role in the initiation and progression of AS [47].…”