Murine Graft-Versus-Host Skin Disease: A Chronologic and Quantitative Analysis of Two Histologic Patterns

Charley, Michael R.; Bangert, Jerry L.; Hamilton, Betty L.; Gilliam, James N.; Sontheimer, Richard D.

doi:10.1111/1523-1747.ep12522551

Cited by 29 publications

(10 citation statements)

References 20 publications

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“…One other strain combination (either LP/J or C57BL/6 spleen cells into the other strain) was reported to also demonstrate scleroderma-like effects (40). The reason that these particular strain combinations induce a scleroderma-like disease is unclear since the minor histocompatibility antigens primarily responsible for the GVH response are unknown.…”

Section: Discussionmentioning

confidence: 99%

A modified model of graft‐versus‐host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease

Ruzek¹,

Jha²,

Ledbetter³

et al. 2004

Arthritis & Rheumatism

110

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Objective. Diffuse systemic sclerosis (SSc; scleroderma) is a debilitating disease characterized by excessive dermal fibrosis with later progression to internal organs. In addition to the fibrotic component, major aspects of the disease include vascular or circulatory involvement and immune dysregulation evidenced by inflammatory cells in affected tissues and production of autoantibodies. Many animal models resembling this disease have been studied, including genetic models in mice and chickens, challenge with chemicals such as bleomycin or vinyl chloride to induce fibrosis, and models of graft-versus-host (GVH)-induced disease using certain strains of mice with differences in minor histocompatibility loci. The present studies were undertaken to determine if alteration of the induction of GVH-induced scleroderma could result in a model that more fully represented the human condition. Methods. Disease was induced by injection of spleen cells from B10.D2 mice into BALB/c mice deficient in mature T and B cells (recombination-activating gene 2 targeted). Dermal thickening, collagen deposition, vasoconstriction, and parameters of immunity were analyzed.Results. Similar to the human disease, this modified GVH model of SSc demonstrated evidence of dermal thickening, particularly in the extremities, progressive fibrosis of internal organs, vasoconstriction and altered expression of vascularity markers in skin and internal organs, early immune activation, inflammation in skin and internal organs, and autoantibody generation.Conclusion. This modified model of GVH-induced SSc exhibits all major components of human disease and is likely to contribute to better understanding of the disease mechanisms and, ultimately, improved treatments for patients.

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Section: Discussionmentioning

confidence: 99%

A modified model of graft‐versus‐host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease

Ruzek¹,

Jha²,

Ledbetter³

et al. 2004

Arthritis & Rheumatism

110

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“…The murine GVHSD employed was previously described by our laboratory in detail (2). In brief, BM cells were obtained by flushing the marrow cavities of the femurs and tibiae of donor mice with PBS.…”

Section: Gvhsd Inductionmentioning

confidence: 99%

“…The mHA mismatch LP/JϾB6 GVHSD model that was employed in the present study has been previously described (2). In this model, recipient B6 mice develop clinical and histopathological evidence of progressive cutaneous GVHD disease (Figs.…”

Section: Skin Lesions Expressed In the Lp/jͼb6 Gvhd Murine Modelmentioning

confidence: 99%

“…Our laboratory has previously demonstrated that T lymphocytes are the primary cellular effectors of epidermal basal cell injury that occurs in the LP/JϾB6 model of early murine GVHD skin lesions (2). To determine whether LT␤R-Ig treatment could inhibit the infiltration of T cells into the skin in this model, immunofluorescence analysis was conducted on posterior neck skin biopsy sections on day 14 after transplantation in all groups.…”

Section: Lt␤r-ig Treatment Inhibits T Cell Homing To Skinmentioning

confidence: 99%

“…In prior studies, our laboratory examined a murine early GVHSD model resulting from minor histocompatibility Ag system (mHA) mismatch (2). Using this model, we previously demonstrated that the infiltration of T cells into the skin is essential for the epidermal basal cell injury pattern that is present in early murine GVHSD lesions (2).…”

mentioning

confidence: 99%

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Blockade of Lymphotoxin Signaling Inhibits the Clinical Expression of Murine Graft-versus-Host Skin Disease

Sontheimer

2004

The Journal of Immunology

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Adhesion molecules are essential for the recruitment of T cells into the skin during the development of graft-vs-host skin disease (GVHSD). However, the mechanisms responsible for the regulation of expression of cutaneous adhesion molecules in this setting are still poorly understood. In this study we blocked lymphotoxin (LT) signaling in a murine model of minor histocompatibility Ag system mismatch GVHSD by using an LTβ receptor-Ig fusion protein (LTβR-Ig). The recipient mice treated with control human Ig developed clinically apparent, severe skin lesions. However, none of the mice treated with LTβR-Ig developed clinical skin disease. The expression of ICAM-1 in cutaneous tissue was also much lower in mice treated with LTβR-Ig than in mice treated with human Ig. Thus, the inhibition of LT signaling via LTβR-Ig treatment appears to be capable of markedly ameliorating the development of GVHSD, possibly by inhibiting the expression of adhesion molecules.

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Murine Models for Graft‐Vs.‐Host Disease

Korngold¹,

Friedman²

2003

Thomas' Hematopoietic Cell Transplantation

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Murine Graft-Versus-Host Skin Disease: A Chronologic and Quantitative Analysis of Two Histologic Patterns

Cited by 29 publications

References 20 publications

A modified model of graft‐versus‐host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease

A modified model of graft‐versus‐host–induced systemic sclerosis (scleroderma) exhibits all major aspects of the human disease

Blockade of Lymphotoxin Signaling Inhibits the Clinical Expression of Murine Graft-versus-Host Skin Disease

Murine Models for Graft‐Vs.‐Host Disease

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