Cutaneous Acute Graft-Versus-Host Disease to Minor Histocompatibility Antigens in a Murine Model: Histologic Analysis and Correlation to Clinical Disease

Ferrara, James L.M.; Guillén, Francisco J.; Sleckman, Barry P.; Burakoff, Steven J.; Murphy, Gëorge F.

doi:10.1111/1523-1747.ep12285612

Cited by 60 publications

(6 citation statements)

References 6 publications

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“…One pathologist analyzed the slides in a blinded fashion to assess the intensity of GVHD. Six parameters were scored for small and large bowel according to a 0- to 5-point scale adapted from Cooke et al ( 20 ) (surface colonocyte lesions or villous blunting, crypt regeneration, crypt epithelial cell apoptosis, crypt loss, lamina propria inflammation, and mucosal ulceration); seven parameters for the liver according a 0- to 3-point scale (portal inflammation, bile ducts lesions, periportal necrosis, endothelialitis, lobular necro-inflammatory activity, zonal necrosis, and sinusoidal lymphocytosis) ( 20 ); three parameters for the skin according to a 0- to 3-point scale described by Ferrara et al (basal cell layer vacuolization, epidermal and follicular dyskeratosis, and epidermal and dermal lymphocytic infiltrate) ( 21 ). Scores of each item were added up to provide a total score for each organ, and scores of each target organ were added up to determine a global histological score for each mouse.…”

Section: Methodsmentioning

confidence: 99%

Simple, Reproducible, and Efficient Clinical Grading System for Murine Models of Acute Graft-versus-Host Disease

et al. 2018

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Acute graft-versus-host disease (aGVHD) represents a challenging complication after allogeneic hematopoietic stem cell transplantation. Despite the intensive preclinical research in the field of prevention and treatment of aGVHD, and the presence of a well-established clinical grading system to evaluate human aGVHD, such a valid tool is still lacking for the evaluation of murine aGVHD. Indeed, several scoring systems have been reported, but none of them has been properly evaluated and they all share some limitations: they incompletely reflect the disease, rely on severity stages that are distinguished by subjective assessment of clinical criteria and are not easy to discriminate, which could render evaluation more time consuming, and their reproducibility among different experimenters is uncertain. Consequently, clinical murine aGVHD description is often based merely on animal weight loss and mortality. Here, we propose a simple scoring system of aGVHD relying on the binary (yes or no) evaluation of five important visual parameters that reflect the complexity of the disease without the need to sacrifice the mice. We show that this scoring system is consistent with the gold standard histological staging of aGVHD across several donor/recipient mice combinations. This system is also a strong predictor of survival of recipient mice when used early after transplant and is highly reproducible between experimenters.

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Section: Methodsmentioning

confidence: 99%

Simple, Reproducible, and Efficient Clinical Grading System for Murine Models of Acute Graft-versus-Host Disease

et al. 2018

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“…30 Seven parameters were scored for the liver according to a 0-to 3-point scale. 30 Three parameters were scored for the skin according to a 0-to 3-point scale described by Ferrara et al 31 For immuno-histological evaluation, sections were stained with antibodies against mouse F4/80 (1:200, ab6640, Abcam) to identify common macrophage antigens, Mrc-1 (1:400, ab64693, Abcam) for M2 phenotype macrophage antigens, and GFP (1:1000, ab6673, Abcam) for GFP antigens. For each retrieved sample, five different microscopic fields at 400× magnification for F4/80, Mrc-1, and GFP count were evaluated.…”

Section: Histopathology and Immunohistochemical Analysismentioning

confidence: 99%

Donor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation

Hanaki

Toyoda

Iwamoto

et al. 2021

Immunity Inflam & Disease

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Introduction: Graft-versus-host disease (GVHD) is frequent and fatal complication following allogeneic hematopoietic stem cell transplantation (HSCT) and characteristically involves skin, gut, and liver. Macrophages promote tissue regeneration and mediate immunomodulation. Macrophages are divided into two different phenotypes, classically activated M1 (pro-inflammatory or immunereactive macrophages) and alternatively activated M2 (anti-inflammatory or immune-suppressive macrophages). The anti-inflammatory effect of M2 macrophage led us to test its effect in the pathophysiology of GVHD. Methods: GVHD was induced in lethally irradiated BALB/c mice. M2 macrophages derived from donor bone marrow (BM) were administered intravenously, while controls received donor BM-mononuclear cells and splenocytes. Animals were monitored for clinical GVHD and analyzed.Results: We confirmed that administering donor BM-derived M2 macrophages attenuated GVHD severity and prolonged survival after HSCT. Moreover, donor BM-derived M2 macrophages significantly suppressed donor T cell proliferation by cell-to-cell contact in vitro. Conclusions: We showed the protective effects of donor-derived M2 macrophages on GVHD and improved survival in a model of HSCT. Our data suggest that donor-derived M2 macrophages offer the potential for cell-based therapy to treat GVHD.

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“…Reports of the ultrastructural changes of skin and gut GVHD have emphasized the point contact of lymphocytes with epithelial cells resulting in epithelial injury. In skin the basal cell layer is most severely involved and in the gut the crypts are the primary area of attack [14,16,33,50]. Changes of cytoplasmic blebs have been reported in the ultrastructural studies of small bile ducts; however, in contrast to those in the colon of our mice, the bile duct blebs were apically, not basally, located [28,29].…”

Section: Discussionmentioning

confidence: 57%

Cellular blebbing in superficial colonic epithelial cells occurring with murine graft-versus-host disease

Eigenbrodt

Kneitz

et al. 1995

Vichows Archiv A Pathol Anat

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Subnuclear blebbing of the superficial colonic epithelium, a rarely described light and electron microscopic change in graft-versus-host disease (GVHD), was studied in a murine model of GVHD. Severity of changes induced by transfer of various donor T cell subsets to irradiated, allogeneic recipients, and association with more severe alterations such as erosions and ulceration were evaluated. By light microscopy the basal region of the superficial enterocytes was greatly expanded by eosinophilic to amphophilic, flocculent, sometimes vacuolated material. By electron microscopy these changes were found to be organelle-poor, cytoplasm-filled protrusions from the basal surface of the epithelium. In this model, helper T cells (CD(4+)-enriched, CD(8+)-depleted T cells) transplanted after high dose irradiation were capable of causing the change suggesting cytokine responses may be involved in mediating the cellular injury seen histologically. Close association of blebbing and erosions suggest the blebbing may be the precursor to epithelial erosion or denudation seen in severe intestinal GVHD.

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Cutaneous Acute Graft-Versus-Host Disease to Minor Histocompatibility Antigens in a Murine Model: Histologic Analysis and Correlation to Clinical Disease

Cited by 60 publications

References 6 publications

Simple, Reproducible, and Efficient Clinical Grading System for Murine Models of Acute Graft-versus-Host Disease

Simple, Reproducible, and Efficient Clinical Grading System for Murine Models of Acute Graft-versus-Host Disease

Donor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation

Cellular blebbing in superficial colonic epithelial cells occurring with murine graft-versus-host disease

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