Short-term treatment with anti-CD3 antibody reduces the development and progression of atherosclerosis in mice | |
Article | |
关键词: REQUIRE GRANZYME-B; MONOCLONAL-ANTIBODY; IN-VIVO; SELF-TOLERANCE; RAPID INDUCTION; CELLS; MECHANISMS; THERAPY; CD3; IMMUNOSUPPRESSION; | |
DOI : 10.1161/CIRCULATIONAHA.106.627430 | |
来源: SCIE |
【 摘 要 】
Background - Atherosclerosis is a chronic inflammatory disease of the large arteries that is the primary cause of heart disease and stroke. Anti-CD3-specific antibodies suppress immune responses by antigenic modulation of the CD3 antibody/T-cell receptor complex. Their unique capacity to restore self-tolerance in a mouse model of diabetes and, importantly, in patients with recent-onset type 1 diabetes involves transforming growth factor-beta-dependent mechanisms via expansion and/or activation of regulatory T cells. We hypothesized that treatment with anti-CD3-specific antibodies might inhibit atherosclerosis development and progression in mice. Methods and Results - Low-density lipoprotein receptor - deficient mice were fed a high-cholesterol diet for 13 or 24 weeks. Anti-CD3 antibody was administered on 5 consecutive days beginning 1 week before or 13 weeks after the high-cholesterol diet was initiated, respectively. Control mice were injected in parallel with phosphate-buffered saline. Anti-CD3 antibody therapy reduced plaque development when administered before a high-cholesterol diet and markedly decreased lesion progression in mice with already established atherosclerosis. We found increased production of the antiinflammatory cytokine transforming growth factor-beta in concanavalin A-stimulated lymph node cells and enhanced expression of the regulatory T-cell marker Foxp3 in spleens of anti-CD3 antibody - treated mice. A higher percentage of apoptotic cells within the plaques of anti-CD3 antibody-treated mice was also observed. Conclusions - Altered disease progression, combined with the emergence of this particular cytokine pattern, indicates that short-term treatment with an anti-CD3 antibody induces a regulatory T-cell phenotype that restores self-tolerance in a mouse model of atherosclerosis.
【 授权许可】
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