Transplantation Models in Human/Mouse Chimeras

Tellides, George; Kirkiles, Nancy; Tereb, Denis A.; Schechner, Jeffrey S.; Wilson, Judith; Lorber, Marc I.; Pober, Jordan S.

doi:10.1007/978-3-642-72140-3_63

Cited by 6 publications

(14 citation statements)

References 15 publications

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“…The animals were housed in microisolator cages and were fed sterilized food and water. Serum IgG levels were determined by sandwich ELISA using reagents from Cappel (Durham, NC) as previously described (22). SCID/beige mice were considered "leaky" at IgG levels Ͼ1 g/ml and excluded from experimental use.…”

Section: Animalsmentioning

confidence: 99%

“…inoculation 5 wk after skin engraftment. The number of circulating human T cells was evaluated by flow cytometry as previously described (22). In brief, heparinized retro-orbital venous samples were obtained 7 days after reconstitution, and the erythrocytes were lysed.…”

Section: Pbmc Isolation and Reconstitutionmentioning

confidence: 99%

“…The other half was snap-frozen in OCT (Miles, Elkhart, IL), and 4-m-thick sections were obtained. Immunostaining was performed as previously described (22). In brief, the sections were fixed in acetone for 10 min and incubated overnight at 4°C in the presence of isotype-matched, nonbinding control Abs or the following primary Abs: mouse anti-human CD3 (UCHT1, IgG1), mouse anti-human CD4 (MT310, IgG1), mouse antihuman CD8 (DK25, IgG1), mouse anti-human CD19 (HD37, IgG1), mouse anti-human CD45RA (4KB5, IgG1), mouse anti-human CD45RO (UCHL1, IgG2a), mouse anti-human CD56 (T199, IgG1), and mouse antihuman CD68 (EBM11, IgG1) from Dako (Carpenteria, CA); mouse antihuman perforin (␦G9, IgG2b) from PharMingen (San Diego, CA); and mouse anti-swine MHC class I (74-11-10, IgG2b) and mouse anti-swine MHC class II (MSA3, IgG2a) from VMRD (Pullman, WA).…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

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Human TNF Can Induce Nonspecific Inflammatory and Human Immune-Mediated Microvascular Injury of Pig Skin Xenografts in Immunodeficient Mouse Hosts

Kirkiles-Smith¹,

Tereb²,

Kim³

et al. 2000

The Journal of Immunology

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TNF activates endothelial cells to express cell surface molecules that are necessary to recruit a local infiltrate of leukocytes. Because the actions of this proinflammatory cytokine are not species restricted, we investigated whether human TNF can up-regulate porcine endothelial adhesion molecules to elicit human T cell infiltration and damage of pig skin xenografts in a chimeric immunodeficient mouse model. We have previously demonstrated the vigorous rejection of human skin allografts and the absence of injury to porcine skin xenografts in human PBMC-SCID/beige mice. Intradermal administration of human TNF at high doses (600 or 2000 ng) caused nonspecific inflammatory damage of pig skin grafts, whereas low concentrations of TNF (60 or 200 ng) resulted in human PBMC-dependent injury of porcine endothelial cells. There was a strong correlation among pig skin xenograft damage, human T cell infiltration, and the TNF-induced up-regulation of swine MHC class I and class II molecules, VCAM-1, and, in particular, the de novo expression of porcine E-selectin. The microvascular damage and leukocytic infiltration elicited by TNF were enhanced by porcine IFN-γ, suggesting that xenografts may be less prone to cytokine-mediated injury due to the species-restricted effects of recipient IFN-γ. Our results indicate that maintenance of a quiescent endothelium, which does not express E-selectin or other activation-dependent adhesion molecules, is important in preventing human anti-porcine T cell xenoresponses in vivo and that TNF signaling molecules and TNF-responsive gene products are appropriate therapeutic targets to protect against human T cell-mediated rejection of pig xenografts.

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Section: Animalsmentioning

confidence: 99%

Section: Pbmc Isolation and Reconstitutionmentioning

confidence: 99%

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

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Human TNF Can Induce Nonspecific Inflammatory and Human Immune-Mediated Microvascular Injury of Pig Skin Xenografts in Immunodeficient Mouse Hosts

Kirkiles-Smith¹,

Tereb²,

Kim³

et al. 2000

The Journal of Immunology

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“…The animals were housed individually in microisolator cages and were fed autoclaved food and water. Serum IgG levels were determined by sandwich ELISA using reagents from Cappel (Durham, NC) as previously described (16). SCID/beige animals were considered "leaky" at IgG levels Ͼ1 g/ml and excluded from experimental use.…”

Section: Animalsmentioning

confidence: 99%

“…Human skin was orthotopically transplanted to SCID/ beige mice as previously described (16,17). This and all subsequent experiments were performed under a protocol approved by the Yale Animal Care and Use Committee.…”

Section: Skin Graftingmentioning

confidence: 99%

IL-11 Protects Human Microvascular Endothelium from Alloinjury In Vivo by Induction of Survivin Expression

Kirkiles-Smith¹,

Mahboubi²,

Plescia³

et al. 2004

The Journal of Immunology

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IL-11 can reduce tissue injury in animal models of inflammation but the mechanism(s) is unknown. When C.B-17 SCID/beige mice bearing human skin grafts are injected i.p. with human PBMC allogeneic to the donor skin, infiltrating T cells destroy human microvessels by day 21. Intradermal injection of human IL-11 (500 ng/day) delays the time course of graft microvessel loss without reducing the extent of T cell infiltration. Protective actions of IL-11 are most pronounced on day 15. IL-11 has no effect on T cell activation marker, effector molecule, cytokine expression, or endothelial ICAM-1 expression. IL-11 up-regulates the expression of survivin, a cytoprotective protein, in graft keratinocytes and endothelial cells. Topical application of survivin antisense oligonucleotide down-regulates survivin expression in both cell types and largely abrogates the protective effect of IL-11. We conclude that in this human transplant model, IL-11 exerts a cytoprotective rather than anti-inflammatory or immunomodulatory effect mediated through induction of survivin.

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Endothelial cell activation by tumor necrosis factor elicits human antiporcine cell-mediated rejection responses

Kirkiles-Smith

Tereb

Kim

et al. 2001

Transplantation Proceedings

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Transplantation Models in Human/Mouse Chimeras

Cited by 6 publications

References 15 publications

Human TNF Can Induce Nonspecific Inflammatory and Human Immune-Mediated Microvascular Injury of Pig Skin Xenografts in Immunodeficient Mouse Hosts

Human TNF Can Induce Nonspecific Inflammatory and Human Immune-Mediated Microvascular Injury of Pig Skin Xenografts in Immunodeficient Mouse Hosts

IL-11 Protects Human Microvascular Endothelium from Alloinjury In Vivo by Induction of Survivin Expression

Endothelial cell activation by tumor necrosis factor elicits human antiporcine cell-mediated rejection responses

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