Immune-inflammatory responses in atherosclerosis: Role of an adaptive immunity mainly driven by T and B cells.
Adaptive immune response plays an important role in atherogenesis. In atherosclerosis, the proinflammatory immune response driven by Th1 is predominant but the anti-inflammatory response mediated mainly by regulatory T cells is also present. The role of Th2 and Th17 cells in atherogenesis is still debated. In the plaque, other T helper cells can be observed such as Th9 and Th22 but is little is known about their impact in atherosclerosis. Heterogeneity of CD4(+) T cell subsets presented in the plaque may suggest for plasticity of T cell that can switch the phenotype dependening on the local microenvironment and activating/blocking stimuli. Effector T cells are able to recognize self-antigens released by necrotic and apoptotic vascular cells and induce a humoral immune reaction. Tth cells resided in the germinal centers help B cells to switch the antibody class to the production of high-affinity antibodies. Humoral immunity is mediated by B cells that release antigen-specific antibodies. A variety of B cell subsets were found in human and murine atherosclerotic plaques. In mice, B1 cells could spontaneously produce atheroprotective natural IgM antibodies. Conventional B2 lymphocytes secrete either proatherogenic IgG, IgA, and IgE or atheroprotective IgG and IgM antibodies reactive with oxidation-specific epitopes on atherosclerosis-associated antigens. A small population of innate response activator (IRA) B cells, which is phenotypically intermediate between B1 and B2 cells, produces IgM but possesses proatherosclerotic properties. Finally, there is a minor subset of splenic regulatory B cells (Bregs) that protect against atherosclerotic inflammation through support of generation of Tregs and production of anti-inflammatory cytokines IL-10 and TGF-β and proapoptotic molecules.
Department of Medical Nanobiotechnology, Pirogov Russian State Medical University, Moscow, Russia; Department of Molecular Genetic Diagnostics and Cell Biology, Institute of Pediatrics, Research Center for Children's Health, Moscow, Russia.
Dimitry A
DA
Chistiakov
Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia; Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia; Department of Biophysics, Biological Faculty, Moscow State University, Moscow, Russia.
Alexander N
AN
Orekhov
Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia; Faculty of Medicine, School of Medical Sciences, University of New South Wales, NSW, Sydney, Australia; School of Medicine, University of Western Sydney, Campbelltown NSW, Australia. Electronic address: y.bobryshev@unsw.edu.au.
Yuri V
YV
Bobryshev
D056704:Adaptive Immunity; D000818:Animals; D000906:Antibodies / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies
Adaptive immunity; Antibody; Atherosclerosis; B cell; Humoral immunity; Inflammation; T cell