Taming Immune and Inflammatory Responses to Treat Atherosclerosis

Furthermore, signals derived from yet other T cell subtypes, such as Th2, T follicular helper cells, and Th17 cells, may also influence lesion composition by producing cytokines, promoting macrophage activation, or providing help to B cells in generating antibodies.[...]adaptive immune mechanisms, Janus-like, can either promote or quell inflammatory responses.Recent work, however, has suggested that native rather than modified low-density lipoprotein stimulates cellular immunity and that a “break to tolerance” to a normal protein, apolipoprotein B, the signature protein of low-density lipoprotein, triggers a selective cellular immune response in experimental atherosclerosis in mice (12).To complete experiments in a reasonable time span, most mouse experiments use exaggerated hyperlipidemia that ignites a drastically accelerated disease process rather far removed from human atherogenesis (13-15).[...]our mouse experiments generally look at single manipulations to modify atherosclerosis, whereas our human patients currently receive potent medications that change the nature of plaques (e.g., statins, blockers of the renin-angiotensin pathway, antiplatelet agents).Inhibition of the EGF receptor now represents a new approach to modulate T cell immunity and combat residual risk in atherosclerotic individuals. 1 L. Jonasson, J. Holm, O. Skalli, G. Gabbiani, G.K. Hansson, Expression of class II transplantation antigen on vascular smooth muscle cells in human atherosclerosis, J Clin Invest, Vol. 76, 1985, 125-131 2 L. Jonasson, J. Holm, O. Skalli, G. Bondjers, G.K. Hansson, Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque, Arteriosclerosis, Vol. 6, 1986, 131-138 3 G.K. Hansson, J. Holm, L. Jonasson, Detection of activated T lymphocytes in the human atherosclerotic plaque, Am J Pathol, Vol. 135, 1989, 169-175 4 G.K. Hansson, L. Jonasson, The discovery of cellular immunity in the atherosclerotic plaque, Arterioscler Thromb Vasc Biol, Vol. 29, 2009, 1714-1717 5 P. Libby, G.K. Hansson, Involvement of the immune system in human atherogenesis: current knowledge and unanswered questions, Lab Invest, Vol. 64, 1991, 5-15 6 A. Gistera, G.K. Hansson, The immunology of atherosclerosis, Nat Rev Nephrol, Vol. 13, 2017, 368-380 7 H.M. Dansky, S.A. Charlton, M.M. Harper, J.D. Smith, T and B lymphocytes play a minor role in atherosclerotic plaque formation in the apolipoprotein E-deficient mouse, Proc Natl Acad Sci U S A, V