Short-Term Treatment With Anti-CD3 Antibody Reduces the Development and Progression of Atherosclerosis in Mice

Steffens, Sabine; Burger, Fabienne; Pelli, Graziano; Dean, Yann; Elson, Greg; Kosco‐Vilbois, Marie H.; Chatenoud, Lucienne; Mach, François

doi:10.1161/circulationaha.106.627430

Cited by 96 publications

(58 citation statements)

References 44 publications

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“…To further substantiate the role of endogenous Treg cells in postischemic neovascularization, we also treated CD28-deficient mice with nonmitogenic anti-CD3 monoclonal antibody to upregulate endogenous Treg cell levels. 21,22 Finally, we analyzed the proangiogenic potential of exogenous Treg cell administration in Rag1-deficient mice with hindlimb ischemia.…”

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confidence: 99%

Regulatory T Cells Modulate Postischemic Neovascularization

et al. 2009

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Background-CD4ϩ and CD8 ϩ T lymphocytes are key regulators of postischemic neovascularization. T-cell activation is promoted by 2 major costimulatory signalings, the B7/CD28 and CD40 -CD40 ligand pathways. Interestingly, CD28 interactions with the structurally related ligands B7-1 and B7-2 are also required for the generation and homeostasis of CD4 ϩ CD25 ϩ regulatory T cells (Treg cells), which play a critical role in the suppression of immune responses and the control of T-cell homeostasis. We hypothesized that Treg cell activation may modulate the immunoinflammatory response to ischemic injury, leading to alteration of postischemic vessel growth. Methods and Results-Ischemia was induced by right femoral artery ligation in CD28-, B7-1/2-, or CD40-deficient mice (nϭ10 per group). CD40 deficiency led to a significant reduction in the postischemic inflammatory response and vessel growth. In contrast, at day 21 after ischemia, angiographic score, foot perfusion, and capillary density were increased by 2.0-, 1.2-, and 1.8-fold, respectively, in CD28-deficient mice, which showed a profound reduction in the number of Treg cells compared with controls. Similarly, disruption of B7-1/2 signaling or anti-CD25 treatment and subsequent Treg deletion significantly enhanced postischemic neovascularization. These effects were associated with enhanced accumulation of CD3-positive T cells and Mac-3-positive macrophages in the ischemic leg. Conversely, treatment of CD28 Ϫ/Ϫ mice with the nonmitogenic anti-CD3 monoclonal antibody enhanced the number of endogenous Treg cells and led to a significant reduction of the postischemic inflammatory response and neovascularization. Finally, coadministration of Treg cells and CD28 Ϫ/Ϫ splenocytes in Rag1 Ϫ/Ϫ mice with hindlimb ischemia abrogated the CD28 Ϫ/Ϫ splenocyte-induced activation of the inflammatory response and neovascularization.

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confidence: 99%

Regulatory T Cells Modulate Postischemic Neovascularization

et al. 2009

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“…When given after 13 wk of diet, there was 71% less progression over 11 wk. The antibody used was engineered to be missing the Fc portion and so was not pro-inflammatory (1677 NS TAP1 (transporter associated with antigenic processing 1) had no effect on atherosclerosis (932). TAP1 transports cytosol-derived antigens into the ER to be loaded onto MHCI which presents antigen to the TCR with the CD8 adapter (expressed on CTL)…”

Section: Cd3mentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

388

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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“…Steffens et al (44) showed that administration of a nonmitogenic anti-CD3 antibody reduced plaque development and markedly inhibited lesion progression in mice with already-established atherosclerosis. This was associated with the induction of a regulatory immune response as revealed by increased production of TGF-b and enhanced expression of Foxp3 in lymph node and spleen cells, respectively.…”

Section: Modulation Of Adaptive T Cell Immunity To Treat In Atherosclmentioning

confidence: 99%

The role of adaptive T cell immunity in atherosclerosis

Mallat

Taleb

Ait‐Oufella

et al. 2009

Journal of Lipid Research

184

139

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There is now solid evidence that T cell adaptive immunity is involved in atherogenesis. While initial studies have focused on the pathogenic arm of the immune response, more recent work clearly suggests an important role for several subsets of regulatory T cells in the protection against lesion development. Here, we review the current knowledge on the role of both pathogenic and regulatory adaptive T cell immunity in atherosclerosis, generated mainly from the study of mouse models of the disease.-Mallat, Z., S. Taleb, H. Ait-Oufella, and A. Tedgui. The role of adaptive T cell immunity in atherosclerosis. J. Lipid Res. 2009. 50: S364-S369.

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Short-Term Treatment With Anti-CD3 Antibody Reduces the Development and Progression of Atherosclerosis in Mice

Cited by 96 publications

References 44 publications

Regulatory T Cells Modulate Postischemic Neovascularization

Regulatory T Cells Modulate Postischemic Neovascularization

Molecular Biology of Atherosclerosis

The role of adaptive T cell immunity in atherosclerosis

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