Primarily Vascularized Allografts of Hearts in Mice

Corry, Robert J.; Winn, Henry J.; Russell, Paul

doi:10.1097/00007890-197310000-00010

Cited by 754 publications

(92 citation statements)

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“…Briefly, fully MHC-mismatched hearts from BALB/c donors (H-2 d ) were transplanted heterotopically into wild-type or p27 kip1Ϫ/Ϫ mice on the C57BL/6 background (H-2 b ). The donor aorta was anastomosed to the recipient abdominal aorta, and the donor pulmonary artery was sutured to the recipient inferior vena cava, as described (17). Graft function was monitored by abdominal palpation, and grafts were harvested at the time of rejection or as indicated.…”

Section: Heterotopic Cardiac Allograftingmentioning

confidence: 99%

The Cyclin-Dependent Kinase Inhibitor p27kip1 Is Required for Transplantation Tolerance Induced by Costimulatory Blockade

Rowell

Wang

Hancock

et al. 2006

The Journal of Immunology

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The cyclin-dependent kinase (CDK) inhibitor p27kip1 is an important negative regulator of the cell cycle that sets a threshold for mitogenic signals in T lymphocytes, and is required for T cell anergy in vitro. To determine whether p27kip1 is required for tolerance in vivo, we performed cardiac allograft transplantation under conditions of combined CD28/CD40L costimulatory blockade. Although this treatment induced long-term allograft survival in wild-type recipients, costimulatory blockade was no longer sufficient to induce tolerance in mice lacking p27kip1. Rejected allografts from p27kip1−/− mice contained more CD4+ T lymphocytes and exhibited more tissue damage than allografts from tolerant, wild-type mice. Infiltrating p27kip1-deficient T cells, but not wild-type T cells, exhibited nuclear expression of cyclins E and A, indicating uncontrolled T cell cycle progression in the graft. The failure of tolerance in p27kip1−/− mice was also accompanied by markedly increased numbers of allospecific, IFN-γ-producing cells in the periphery, and occurred despite apparently normal regulatory T cell activity. These data demonstrate that the CDK inhibitor p27kip1 enforces the costimulatory requirement for the expansion and differentiation of alloimmune effector T lymphocytes in vivo, and point to CDKs as novel targets for immunosuppressive or tolerance-inducing therapies.

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Section: Heterotopic Cardiac Allograftingmentioning

confidence: 99%

The Cyclin-Dependent Kinase Inhibitor p27kip1 Is Required for Transplantation Tolerance Induced by Costimulatory Blockade

Rowell

Wang

Hancock

et al. 2006

The Journal of Immunology

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“…Intra-abdominal heterotopic cardiac transplantation was performed, as previously described by Corry et al (14). Briefly, a median sternotomy was performed on the donor, and the heart graft was slowly perfused in situ with 1.0 ml of cold heparinized Ringer's lactate solution through the inferior vena cava and aorta before the superior vena cava and pulmonary veins were ligated and divided.…”

Section: Heterotopic Cardiac Transplantationmentioning

confidence: 99%

Cytokines Regulate the Pattern of Rejection and Susceptibility to Cyclosporine Therapy in Different Mouse Recipient Strains After Cardiac Allografting

Wang

Hosiawa

Min

et al. 2003

The Journal of Immunology

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We determined the role of cytokines in regulating the pattern of rejection and recipient susceptibility to cyclosporine (CsA) in a mouse cardiac allograft model. Hearts from C3H mice transplanted into untreated BALB/c (Th2-dominant) and C57BL/6 (Th1-dominant) mice showed different patterns of rejection. C3H allografts in BALB/c mice showed typical acute vascular rejection (AVR) with strong intragraft deposition and high serum levels of anti-donor IgG with predominant IgG1, while C3H allografts in C57BL/6 mice showed typical acute cellular rejection (ACR) with massive intragraft infiltration of CD4+ and CD8+ lymphocytes and low serum levels of anti-donor IgG with predominant IgG2a. Elevated intragraft mRNA expression of IL-2, IFN-γ, and IL-12 mRNA was present in C57BL/6 recipients, whereas allografts in BALB/c mice displayed increased IL-4 and IL-10 mRNA levels. CsA therapy completely inhibited ACR and induced indefinite allograft survival in C57BL/6 recipients, while the same therapy failed to prevent AVR, and only marginally prolonged graft survival in BALB/c recipients. In contrast, rapamycin blocked AVR, achieving indefinite survival in BALB/c recipients, but was less effective at preventing ACR in C57BL/6 recipients. The disruption of the IL-12 or IFN-γ genes in C57BL/6 mice shifted ACR to AVR, and resulted in concomitant recipient resistance to CsA therapy. Conversely, disruption of IL-4 gene in BALB/c mice markedly attenuated AVR and significantly prolonged allograft survival. These data suggest that the distinct cytokine profiles expressed by different mouse strains play an essential role in regulating the pattern of rejection and outcome of CsA/rapamycin therapy.

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“…Lipid-mediated gene transfer of cardiac allografts Heterotopic cardiac transplantation was performed by anastomosing BALB/c donor hearts to the great vessels in the abdomen of C57BL/6 recipients as described by Corry et al 47 For vIL-10 gene transfer, donor hearts were perfused in situ by ligating the venae cavae to retain the perfusate. The distal aortic arch was then ligated and held in position by the suture to facilitate perfusion of the coronary vasculature via the aortic root with a 1 cc syringe and a 30-gauge needle.…”

Section: Plasmids and Lipidmentioning

confidence: 99%

Lipid-mediated gene transfer of viral IL-10 prolongs vascularized cardiac allograft survival by inhibiting donor-specific cellular and humoral immune responses

DeBruyne

Chan

et al. 1998

Gene Ther

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Primarily Vascularized Allografts of Hearts in Mice

Cited by 754 publications

References 0 publications

The Cyclin-Dependent Kinase Inhibitor p27kip1 Is Required for Transplantation Tolerance Induced by Costimulatory Blockade

The Cyclin-Dependent Kinase Inhibitor p27kip1 Is Required for Transplantation Tolerance Induced by Costimulatory Blockade

Cytokines Regulate the Pattern of Rejection and Susceptibility to Cyclosporine Therapy in Different Mouse Recipient Strains After Cardiac Allografting

Lipid-mediated gene transfer of viral IL-10 prolongs vascularized cardiac allograft survival by inhibiting donor-specific cellular and humoral immune responses

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