Induction of GVHD-Like Skin Disease by Passively Transferred CD8+ T-Cell Receptor Transgenic T Cells into Keratin 14-Ovalbumin Transgenic Mice

Shibaki, Akihiko; Sato, Atsushi; Vogel, Jonathan; Miyagawa, Fumi; Katz, Stephen I.

doi:10.1111/j.0022-202x.2004.22701.x

Cited by 72 publications

(111 citation statements)

References 32 publications

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“…Our results are supported by two recent reports. Shibaki et al (29) used mice expressing the whole OVA protein under the K14 promoter and showed that DCs emigrating from skin explants cross-presented OVA peptides. DCs emigrating from whole skin explants are a mixture of dermal DCs and LCs (30), and therefore, the relative contribution of LCs could not be determined in this report.…”

Section: Discussionmentioning

confidence: 99%

Langerhans cells cross-present antigen derived from skin

Stoitzner

Tripp²,

Eberhart

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

181

148

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Section: Discussionmentioning

confidence: 99%

Langerhans cells cross-present antigen derived from skin

Stoitzner

Tripp²,

Eberhart

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

181

148

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“…The LC paradigm has been expanded to include LC that migrate to skin-draining LN in the steady state in the absence of activating stimuli where they present self-peptides to T cells [10][11][12][13][14]. This steady-state presentation of self-antigens has been proposed to eliminate self-reactive T cells and provide a mechanism of peripheral tolerance [15,16].…”

Section: Mini-reviewmentioning

confidence: 99%

“…In addition, they dramatically upregulate their surface expression of co-stimulatory molecules and start to produce cytokines required for proper Th1 or Th2 instruction. Thus, by the time LC arrive in the LN, they have acquired the surface phenotype of a 'functionally' mature DC capable of activating naive T cells and thereby initiating an adaptive immune response specifically tailored to fight off the invading cutaneous pathogen [5].The LC paradigm has been expanded to include LC that migrate to skin-draining LN in the steady state in the absence of activating stimuli where they present self-peptides to T cells [10][11][12][13][14]. This steady-state presentation of self-antigens has been proposed to eliminate self-reactive T cells and provide a mechanism of peripheral tolerance [15,16].…”

mentioning

confidence: 99%

Insights into Langerhans cell function from Langerhans cell ablation models

2008

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Langerhans cells (LC) are the principal dendritic cell (DC) population in the epidermis of the skin. Owing to their prominent position at the environmental barrier, LC have long been considered to be prototypic sentinel DC. More recently, the precise role of LC in the initiation and control of cutaneous immune responses has become debatable. To elucidate their contribution to immune regulation in the skin, our laboratories have generated genetically modified mice in which LC can be followed in situ by expression of enhanced green fluorescent protein and can be either inducibly or constitutively depleted in vivo. This review highlights the similarities and differences between these mouse models, discusses the discovery and functional significance of Langerin 1 dermal DC, and examines some recent data that help to shed light on LC function. The Langerhans cell paradigmLangerhans cells (LC) were discovered by Paul Langerhans in 1868 [1], but it took more than 100 years before they were first associated with the immune system and recognized as antigenpresenting cells [2]. In particular, Ralph Steinman's group [3] dissected the functional characteristics of LC starting from the seminal finding that murine epidermal LC mature into potent immunostimulatory dendritic cells (DC) in vitro. The work that followed shaped the concept of DC as professional inducers of T-cell immune responses largely by studying LC, though the term 'LC paradigm' was coined much later by Wilson and Villadangos [4].This concept assigned three key functions to LC/DC (reviewed in [5]). First, immature LC that reside in the periphery in the steady state are highly specialized in antigen uptake. LC form a dense network in the epidermis where they constantly scan the environment by extending and retracting their dendrites and are ideally positioned to detect any pathogen breaching the skin barrier [6]. Second, LC transport antigen to skindraining lymph nodes (LN), which is essential to ensure interaction with rare antigen-specific naive T cells. Stimulation by a number of pathogen products in addition to pro-inflammatory cytokines induces LC activation [7][8][9]. Activated LC downregulate expression of E-cadherin, which is thought to maintain their position in the epidermis, and begin to express CC Correspondence: Daniel Kaplan e-mail: DanKaplan@umn.edu Eur. J. Immunol. 2008. 38: 2369-2376 DOI 10.1002 HIGHLIGHTS 2369 Mini-Reviewwww.eji-journal.eu chemokine receptor 7, which guides the cells to the T-cell areas in the LN. Third, during migration the LC undergo a process of maturation in which they process antigen acquired in the skin and present it in the context of MHC class I/II. In addition, they dramatically upregulate their surface expression of co-stimulatory molecules and start to produce cytokines required for proper Th1 or Th2 instruction. Thus, by the time LC arrive in the LN, they have acquired the surface phenotype of a 'functionally' mature DC capable of activating naive T cells and thereby initiating an adaptive immune response specif...

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“…We used a pCMV␤ expression vector (Invitrogen, Carlsbad, CA) that contained the cytomegalovirus (CMV) promoter, the simian virus 40 (SV40) splice donor/splice acceptor site, the lacZ gene, and the SV40 polyadenylation signal. We selected human keratin 14 (K14), 10 the mouse pro-␣ 2 chain of type I collagen (col1a2), 11 or the CMV promoter for epidermis-specific, dermis-specific, or ubiquitous expression of the transgene, respectively. We first modified pCMV␤ by replacing LacZ with human fulllength COL7A1 cDNA, and the CMV promoter with the human K14 or the mouse col1a2 gene.…”

Section: Generation Of Transgenic Micementioning

confidence: 99%

“…10,11 The mice with K14 or col1a2 promoters were designated as K14Tg mice (COL7 K14-hϩ ) and col1a2Tg mice (COL7 col1-hϩ ), respectively ( Figure 1A). In addition, the ubiquitous CMV promoter was used to generate transgenic mice with both epidermal and dermal expression (CMVTg mice: COL7 CMV-hϩ ) ( Figure 1A).…”

Section: Generation Of Transgenic Mice Showing Keratinocyte-or Fibrobmentioning

confidence: 99%

Keratinocyte-/Fibroblast-Targeted Rescue of Col7a1-Disrupted Mice and Generation of an Exact Dystrophic Epidermolysis Bullosa Model Using a Human COL7A1 Mutation

Ito

Sawamura

Goto

et al. 2009

The American Journal of Pathology

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Recessive dystrophic epidermolysis bullosa (RDEB) is a severe hereditary bullous disease caused by mutations in COL7A1, which encodes type VII collagen (COL7). Col7a1 knockout mice (COL7 m؊/؊ ) exhibit a severe RDEB phenotype and die within a few days after birth. Toward developing novel approaches for treating patients with RDEB, we attempted to rescue COL7 m؊/؊ mice by introducing human COL7A1 cDNA. We first generated transgenic mice that express human COL7A1 cDNA specifically in either epidermal keratinocytes or dermal fibroblasts. We then performed transgenic rescue experiments by crossing these transgenic mice with COL7 m؉/؊ heterozygous mice. Surprisingly, human COL7 expressed by keratinocytes or by fibroblasts was able to rescue all of the abnormal phenotypic manifestations of the COL7 m؊/؊ mice, indicating that fibroblasts as well as keratinocytes are potential targets for RDEB gene therapy. Furthermore, we generated transgenic mice with a premature termination codon expressing truncated COL7 protein and performed the same rescue experiments. Notably, the COL7 m؊/؊ mice rescued with the human COL7A1 allele were able to survive despite demonstrating clinical manifestations very similar to those of human RDEB, indicating that we were able to generate surviving animal models of RDEB with a mutated human COL7A1 gene. This model has great potential for future research into the pathomechanisms of dystrophic epidermolysis bullosa and the development of gene therapies for patients with dystrophic epidermolysis bullosa. Dystrophic epidermolysis bullosa (DEB) is clinically characterized by mucocutaneous blistering in response to minor trauma, followed by scarring and nail dystrophy. The blistering occurs along the epidermal basement membrane zone (BMZ) just beneath the lamina densa at the level of the anchoring fibrils. The inheritance of DEB can be autosomal dominant (DDEB) or autosomal recessive (RDEB), each comprising subtypes of different clinical presentations and severities.1 Both DDEB and RDEB are known to be caused by mutations in the COL7A1 gene encoding type VII collagen (COL7), the major component of anchoring fibrils.2 The most severe RDEB subtype, the Hallopeau-Siemens subtype, shows a complete lack of expression of type VII collagen, whereas a less severe RDEB subtype, the non-Hallopeau-Siemens subtype, shows some collagen expression. The clinical fea-

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Induction of GVHD-Like Skin Disease by Passively Transferred CD8+ T-Cell Receptor Transgenic T Cells into Keratin 14-Ovalbumin Transgenic Mice

Cited by 72 publications

References 32 publications

Langerhans cells cross-present antigen derived from skin

Langerhans cells cross-present antigen derived from skin

Insights into Langerhans cell function from Langerhans cell ablation models

Keratinocyte-/Fibroblast-Targeted Rescue of Col7a1-Disrupted Mice and Generation of an Exact Dystrophic Epidermolysis Bullosa Model Using a Human COL7A1 Mutation

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