Mouse Vascular Endothelium Activates CD8+ T Lymphocytes in a B7-Dependent Fashion

Kreisel, Daniel; Krupnick, Alexander S.; Balsara, Keki R.; Riha, Markus; Gelman, Andrew E.; Popma, Sicco H.; Szeto, Wilson Y.; Turka, Laurence A.; Rosengard, Bruce R.

doi:10.4049/jimmunol.169.11.6154

Cited by 70 publications

(50 citation statements)

References 44 publications

(50 reference statements)

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“…45 Murine ECs activate CD8 ϩ but not CD4 ϩ effector T cells, even when they are induced to express class II MHC molecules in response to IFN-␥. 46,47 Instead, IFN-␥-treated murine ECs may predominantly activate CD4 ϩ CD25 ϩ regulatory T cells, 48 a finding we have not been able to replicate with human ECs (J.S. Pober, unpublished observations, 2006).…”

Section: Control Of Ifn-␥ Synthesis In Gamentioning

confidence: 87%

Interferon-γ Axis in Graft Arteriosclerosis

Tellides

Pober

2007

Circulation Research

104

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Abstract-Cardiac transplantation is the most effective treatment for advanced heart failure. Despite improvements in immunosuppression therapy that prevent acute rejection, cardiac allografts fail at rates of 3% to 5% per posttransplant year. The hallmark morphological lesion of chronically failing cardiac allografts, also seen in chronic renal and liver graft failure, is luminal stenosis of blood vessels, especially of conduit arteries. Late graft failure results from widespread secondary ischemic injury to the graft parenchyma rather than direct immune-mediated damage. Although this process affects the entire graft vasculature, graft arteriosclerosis is a suitable term to describe the problem because it applies to different types of failing organs and because it emphasizes the central feature, namely an accelerated form of arterial injury and remodeling. The precise pathogenesis of graft arteriosclerosis is unknown. In this review, we make the case that the signature T-helper type 1 cytokine, interferon (IFN)-␥, is a key effector in graft arteriosclerosis, which, together with the IFN-␥-inducing cytokine interleukin-12 and IFN-␥-inducible chemokines such as CXCR3 ligands, constitute a positive feedback loop for T-cell activation, differentiation, and recruitment that we refer to as the IFN-␥ axis. We evaluate the evidence to support this hypothesis in clinical observational and experimental animal studies. Additionally, we examine the regulation of IFN-␥ production within the artery wall, the effects of IFN-␥ on vessel wall cells, and the outcome of therapeutic agents on IFN-␥ production and signaling. These observations lead us to suggest that new therapies for graft arteriosclerosis should be optimized which focus on reducing IFN-␥ synthesis or actions. (Circ Res. 2007;100:622-632.)

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Section: Control Of Ifn-␥ Synthesis In Gamentioning

confidence: 87%

Interferon-γ Axis in Graft Arteriosclerosis

Tellides

Pober

2007

Circulation Research

104

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“…Thus, our results point to a variable role of CCR7 for direct alloantigen-specific T cell priming, depending on the occurrence of the alloantigen within or outside the context of secondary lymphoid organs. Secondly, nonhematopoietic cells within allografts can also directly activate T cells and thereby provide another mecha-nisms of allogeneic priming independent of secondary lymphoid organs [19,20].…”

Section: Discussionmentioning

confidence: 99%

“…endothelial cells, transferred within an allogeneic organ are essential for direct presentation of the respective alloantigens and direct stimulation of effector cells involved in graft rejection [18][19][20]. To further elucidate the role of donor leukocytes in an allogeneic tumor rejection model, we modified our experimental set up by inducing tumor growth of MCA205 cells (H2-b) first in a syngeneic C57BL/6 background to induce population of the tumors with leukocytes.…”

Section: Solid Tumor Grafts Elucidate the Role Of Donor Apc In Ccr7-dmentioning

confidence: 99%

The chemokine receptor CCR7 controls lymph node‐dependent cytotoxic T cell priming in alloimmune responses

Höpken

Droese

et al. 2004

Eur J Immunol

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The chemokine receptor CCR7 and its ligands regulate migration and colocalization of T cells and mature dendritic cells to and within secondary lymphoid organs. The requirement of CCR7 in efficient priming of allospecific cytotoxic CD8 + T cells is poorly characterized. Here, we demonstrate a role for CCR7 in the initiation of an alloimmune response and in the development of transplant rejection. Remarkably, in a model of acute allogeneic tumor rejection, CCR7 -/-mice completely failed to reject subcutaneously injected MHC class I mismatched tumor cells and cytotoxic activity of allospecific T cells was severely compromised. When solid tumors derived from wild-type mice were transplanted, recipient CCR7 -/-mice were capable of rejecting the allografts. In contrast, tumor allografts transplanted from CCR7 -/-donors onto CCR7 -/-recipients showed allograft survival up to 28 days, suggesting a critical function of CCR7 on donor-type passenger leukocytes in the initiation of cytotoxic CD8 + T cell responses. In a heterotopic heart transplantation model CCR7 deficiency resulted in significantly prolonged but not indefinite allograft survival. Additional prolongation of graft survival was observed when hearts from CCR7 -/-mice were used as donor organs. Our results define a key role for CCR7 in allogeneic T cell priming within the context of draining lymph nodes.

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“…Endothelial cells and CD4 ϩ T cells were isolated from thoracic aorta and pooled splenocytes, respectively (1)(2)(3)(4).…”

Section: Animals and Cell Isolationmentioning

confidence: 99%

“…We have shown that endothelial cells can act as APCs to allogeneic CD8 ϩ T lymphocytes and can trigger allograft rejection via CD8 ϩ direct allorecognition (2,3). However, despite expression of both inducible MHC class II and costimulatory molecules, vascular endothelium is unable to induce cell division in allogeneic CD4 ϩ T cells in vitro or in vivo (4,5).…”

mentioning

confidence: 99%

Cutting Edge: Murine Vascular Endothelium Activates and Induces the Generation of Allogeneic CD4+25+Foxp3+ Regulatory T Cells

Krupnick¹,

Gelman

Barchet

et al. 2005

The Journal of Immunology

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141

124

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Unlike graft-resident donor-derived hemopoietic APCs, which decrease in number over time after transplantation, vascular endothelial cells are lifelong residents of a vascularized allograft. Endothelial cells are potent APCs for allogeneic CD8+ T lymphocytes but are unable to induce proliferation of allogeneic CD4+ T lymphocytes. Although the reason for this differential response has been poorly understood, here we report that alloantigen presentation by vascular endothelium to CD4+ T lymphocytes activates and induces CD4+25+Foxp3+ regulatory T cells, which can inhibit proliferation of alloreactive T cells both in vitro and in vivo. This process occurs independently of B7.1 costimulation but is dependent on programmed death ligand 1 (B7-H1). This finding may have important implications for tolerance induction in transplantation.

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Mouse Vascular Endothelium Activates CD8+ T Lymphocytes in a B7-Dependent Fashion

Cited by 70 publications

References 44 publications

Interferon-γ Axis in Graft Arteriosclerosis

Interferon-γ Axis in Graft Arteriosclerosis

The chemokine receptor CCR7 controls lymph node‐dependent cytotoxic T cell priming in alloimmune responses

Cutting Edge: Murine Vascular Endothelium Activates and Induces the Generation of Allogeneic CD4+25+Foxp3+ Regulatory T Cells

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