T Lymphocyte Autoreactivity in Inflammatory Mechanisms Regulating Atherosclerosis
Schematic representation of T lymphocyte subset activation within atherosclerotic plaque. Different self-structures are expressed in the intima of the vessel wall and subjected to enzymatic/oxidative modifications. These modified molecules are taken up by dendritic cells and presented to CD4+ T helper cells via MHC class II molecules. Antigen presentation promotes T lymphocyte activation and secretion of different cytokines. Effector CD4+ Th1 cells produce pro-inflammatory cytokines, particularly IFN-γ, with proatherogenic effects. Activated Th2 lymphocytes secrete IL-4 and IL-5 which promote the differentiation of B cells in plasma cells and the production of specific antibodies. Some infiltrated T cells upon activation differentiate in Th17 lymphocytes characterized by the production of IL-17, but their role remains controversial. Regulatory T cells (Tregs) downregulate inflammation by secretion of TGF-β and IL-10. The pro-inflammatory mediators released by activated T cells reduce the stability of the lesion promoting plaque rupture and thrombotic events.