Immunoglobulin Leakiness in scid Mice with CD4+ T-Cell-Induced Chronic Colitis

Brimnes, Jens; Reimann, Jörg; Claësson, Mogens H.

doi:10.1006/clim.2000.4891

Cited by 8 publications

(9 citation statements)

References 25 publications

(27 reference statements)

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“…However, our recent investigations indicate that immunoglobulins do not contribute to the pathogenesis of IBD in CD4 + T cell transplanted scid mice [14], and we have not been able to demonstrate reactivity against enterobacterial antigens (data not published). In the present study we have focused on the role of enteric bacterial antigens in the activation of CD4 + T cells from scid mice with IBD.…”

Section: Discussionmentioning

confidence: 68%

“…Subsequently, the scid host develops a colitis characterized by elongation, degeneration and abscesses of the crypts, giant cell formation, epithelial ulcerations and the presence of elevated numbers of CD4 + T cells in the colonic lamina propria (LP) [8,11]. We have previously demonstrated that the colitis is accompanied by a high production of host-derived (leaky) immunoglobulins [8,13], the levels of which, however, do not correlate with disease severity [14]. So far, we have not been able to determine the antigen specificity of these immunoglobulins.…”

Section: Introductionmentioning

confidence: 99%

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Enteric bacterial antigens activate CD4+ T cells fromscid mice with inflammatory bowel disease

et al. 2001

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Enteric bacterial antigens activate CD4+ T cells fromscid mice with inflammatory bowel disease

et al. 2001

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“…A dot blot assay using digested fecal samples was performed as previously described [28] with slight modification. In short, mice were fed Western Diet for 1½ weeks and fecal samples were collected and stored at −20°C.…”

Section: Methodsmentioning

confidence: 99%

Characteristics of Multi-Organ Lymphangiectasia Resulting from Temporal Deletion of Calcitonin Receptor-Like Receptor in Adult Mice

2012

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Adrenomedullin (AM) and its receptor complexes, calcitonin receptor-like receptor (Calcrl) and receptor activity modifying protein 2/3, are highly expressed in lymphatic endothelial cells and are required for embryonic lymphatic development. To determine the role of Calcrl in adulthood, we used an inducible Cre-loxP system to temporally and ubiquitously delete Calcrl in adult mice. Following tamoxifen injection, Calcrlfl/fl/CAGGCre-ER™ mice rapidly developed corneal edema and inflammation that was preceded by and persistently associated with dilated corneoscleral lymphatics. Lacteals and submucosal lymphatic capillaries of the intestine were also dilated, while mesenteric collecting lymphatics failed to properly transport chyle after an acute Western Diet, culminating in chronic failure of Calcrlfl/fl/CAGGCre-ER™ mice to gain weight. Dermal lymphatic capillaries were also dilated and chronic edema challenge confirmed significant and prolonged dermal lymphatic insufficiency. In vivo and in vitro imaging of lymphatics with either genetic or pharmacologic inhibition of AM signaling revealed markedly disorganized lymphatic junctional proteins ZO-1 and VE-cadherin. The maintenance of AM signaling during adulthood is required for preserving normal lymphatic permeability and function. Collectively, these studies reveal a spectrum of lymphatic defects in adult Calcrlfl/fl/CAGGCre-ER™ mice that closely recapitulate the clinical symptoms of patients with corneal, intestinal and peripheral lymphangiectasia.

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“…It has been reported that such leakiness is higher in mice housed under nonspecific pathogen-free conditions, which is the type of facility in which we house our mice, and leakiness is generally higher on the C57BL/6 genetic background. [38][39][40] The FVIII null mice crossed with NSG mice were on a mixed genetic background of C57BL/6 and 129/SV, so NSGF8KO mice inherited a mixed genetic background of C57BL/6, 129/SV, and NOD. Backcrossing NSGF8KO mice to a pure NOD background will need to be pursued in future studies.…”

Section: Human Thrombocytopoiesis In the 2bf8lv Genetically Modified mentioning

confidence: 99%

Platelet gene therapy corrects the hemophilic phenotype in immunocompromised hemophilia A mice transplanted with genetically manipulated human cord blood stem cells

Shi

Kuether

Chen

et al. 2014

Blood

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Key Points• Platelet-specific lentiviral gene delivery to human hematopoietic stem cells can efficiently introduce FVIII expression in human platelets.• Human platelet-derived FVIII can ameliorate the hemophilic phenotype in an immunocompromised hemophilia A mouse model.Our previous studies have demonstrated that platelet FVIII (2bF8) gene therapy can improve hemostasis in hemophilia A mice, even in the presence of inhibitory antibodies, but none of our studies has targeted human cells. Here, we evaluated the feasibility for lentivirus (LV)-mediated human platelet gene therapy of hemophilia A. Human platelet FVIII expression was introduced by 2bF8LV-mediated transduction of human cord blood (hCB) CD34 1 cells followed by xenotransplantation into immunocompromised NSG mice or NSG mice in an FVIII null background (NSGF8KO). Platelet FVIII was detected in all recipients that received 2bF8LV-transduced hCB cells as long as human platelet chimerism persisted. All NSGF8KO recipients (n 5 7) that received 2bF8LV-transduced hCB cells survived tail clipping if animals had greater than 2% of platelets derived from 2bF8LV-transduced hCB cells, whereas 5 of 7 survived when human platelets were 0.3% to 2%. Whole blood clotting time analysis confirmed that hemostasis was improved in NSGF8KO mice that received 2bF8LV-transduced hCB cells. We demonstrate, for the first time, the feasibility of 2bF8LV gene delivery to human hematopoietic stem cells to introduce FVIII expression in human platelets and that human platelet-derived FVIII can improve hemostasis in hemophilia A. (Blood. 2014;123(3):395-403)

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Immunoglobulin Leakiness in scid Mice with CD4+ T-Cell-Induced Chronic Colitis

Cited by 8 publications

References 25 publications

Enteric bacterial antigens activate CD4+ T cells fromscid mice with inflammatory bowel disease

Enteric bacterial antigens activate CD4+ T cells fromscid mice with inflammatory bowel disease

Characteristics of Multi-Organ Lymphangiectasia Resulting from Temporal Deletion of Calcitonin Receptor-Like Receptor in Adult Mice

Platelet gene therapy corrects the hemophilic phenotype in immunocompromised hemophilia A mice transplanted with genetically manipulated human cord blood stem cells

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