IFN-γ and Fas/FasL pathways cooperate to induce medial cell loss and neointimal lesion formation in allograft vasculopathy

Hart-Matyas, Michael; Nejat, Sara; Jordan, J.L.; Hirsch, Gregory M.; Lee, Timothy D.G.

doi:10.1016/j.trim.2009.10.004

Cited by 18 publications

(13 citation statements)

References 56 publications

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“…37 Furthermore, it has recently been shown that IFN-␥ and the Fas/FasL pathways cooperate in the development of transplant associated vasculopathy. 38 Thus, an inhibition of IFN-␥ production does appear to be consistent with the protective effects mediated by this population of alloantigendriven adaptive Tregs.…”

Section: Discussionmentioning

confidence: 65%

CD4+ Regulatory T Cells Generated in Vitro with IFN-γ and Allogeneic APC Inhibit Transplant Arteriosclerosis

Warnecke

Feng

Goto

et al. 2010

The American Journal of Pathology

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We have developed a method to generate alloreactive regulatory T cells in vitro in the presence of interferon (IFN)-␥ and donor antigen presenting cells (APCs؊ CD4 ؉ effectors resulted in 29.7 ؎ 14.5% luminal occlusion of allogeneic aortic grafts after 30 days. Cotransfer of Tcon reduced this occlusion to 11.7 ؎ 13.1%; P < 0.05. In addition, the CD31 ؊ donor endothelium was fully repopulated by CD31؉ recipient endothelial cells in the absence of Tcon, but not in the presence of Tcon. In some experiments, we cotransplanted B6 skin with aortic grafts to ensure enhanced reactivation of the regulatory cells, which led to an additional reduction in vasculopathy (1.9 ؎ 3.0% luminal occlusion). In the presence of Tcon, CD4؉ T cell infiltration into grafts was markedly reduced by a regulatory mechanism that included reduced priming and proliferation of CD25 ؊ CD4؉ effectors. These data illustrate the potential of ex vivo generated regulatory T cells for the inhibition of transplant-associated vasculopathy. (Am J

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Section: Discussionmentioning

confidence: 65%

CD4+ Regulatory T Cells Generated in Vitro with IFN-γ and Allogeneic APC Inhibit Transplant Arteriosclerosis

Warnecke

Feng

Goto

et al. 2010

The American Journal of Pathology

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“…Apoptosis of SMCs is a signal for the differentiation of vascular progenitor cells to compensate for the loss of cells. Matyas reported that IFN-γ, secreted by CD8 + T cells, induces apoptosis of SMCs by activating the Fas/Fasl killing pathway [47]. The events that mediate the destruction of SMCs occur in a loop -they continue to promote arterial remodeling even in the absence of persistent allogeneic exposure after an initial exposure.…”

Section: Medial Apoptosismentioning

confidence: 99%

Mechanism of arterial remodeling in chronic allograft vasculopathy

2011

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Chronic allograft vasculopathy (CAV) remains a major obstacle for long-term survival of grafts even though therapeutic strategies have improved considerably in recent years. CAV is characterized by concentric and diffuse neointimal formation, medial apoptosis, infiltration of lymphocyte or inflammatory cells, and deposition of extracellular matrix both in arteries and veins. Recent studies have shown that stem cells derived from the recipient contribute to neointimal formation under the regulation of chemokines and cytokines. Arterial remodeling in allografts eventually causes ischemic graft failure. The pathogenesis is multi-factorial with both immunologic and non-immunological factors being involved. The immunological factors have been discussed extensively in other articles. This review focuses mainly on the arterial remodeling that occurs in 3 layers of vessel walls including intimal injury, accumulation of smooth muscle-like cells in the neointimal, medial smooth muscle cell apoptosis, adventitial fibrosis, and deposition of extracellular matrix.

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“…The underlying media was almost devoid of SMCs, corresponding to the described disappearance of graft SMCs by cytotoxic T cell-mediated apoptosis in this type of model. 14 …”

Section: Balb/c Allografts Transplanted Into Apoementioning

confidence: 99%

Flanking Recipient Vasculature, Not Circulating Progenitor Cells, Contributes to Endothelium and Smooth Muscle in Murine Allograft Vasculopathy

Hagensen

Shim

Falk

et al. 2011

ATVB

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Objective-The prevailing view assumes that circulating endothelial and smooth muscle progenitor cells participate in allograft vasculopathy (AV), although the seminal studies in the field were not designed to distinguish between circulating and migrating cells of recipient origin. We developed a double-transplantation technique to overcome this problem and reinvestigated the origin of endothelial cells (ECs) and smooth muscle cells (SMCs) in murine AV. Methods and Results-Carotid artery segments from BALB/c mice were allografted to apolipoprotein E Ϫ/Ϫ B6 mice with or without a "flanking" isograft interpositioned between the allograft and the recipient artery. Either recipient mice or interpositioned isografts expressed enhanced green fluorescent protein, and consequently, cells migrating into the allograft from the flanking vasculature could easily be tracked and distinguished from recruited circulating cells.

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IFN-γ and Fas/FasL pathways cooperate to induce medial cell loss and neointimal lesion formation in allograft vasculopathy

Cited by 18 publications

References 56 publications

CD4+ Regulatory T Cells Generated in Vitro with IFN-γ and Allogeneic APC Inhibit Transplant Arteriosclerosis

CD4+ Regulatory T Cells Generated in Vitro with IFN-γ and Allogeneic APC Inhibit Transplant Arteriosclerosis

Mechanism of arterial remodeling in chronic allograft vasculopathy

Flanking Recipient Vasculature, Not Circulating Progenitor Cells, Contributes to Endothelium and Smooth Muscle in Murine Allograft Vasculopathy

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