The detection of apoptosis in a human in vitro skin explant assay for graft versus host reactions

Jarvis, Mark; Dickinson, Anne M.; Sviland, Lisbet; Jackson, GH; Konur, Abdo; Wang, X N; Hromadníková, Ilona; Kolb, H. J.; Eißner, Günther; Holler, Ernst

doi:10.1136/jcp.55.2.127

Cited by 29 publications

(15 citation statements)

References 23 publications

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“…In another study, peripheral blood mononuclear cells (PBMC) from bone marrow transplant donors were cultured with the recipient’s irradiated lymphocytes and then cocultured with skin explants obtained from the recipient. Significant epidermal damage, including apoptosis of epidermal keratinocytes, resembling that in drug rash or SJS/TEN was observed 49,50 . This phenomenon could be reproduced in cell‐free supernatants from allostimulated PBMC, and the epidermal damage inhibited by the addition of anti‐TNF‐α or anti‐IFN‐γ antibody 50 .…”

Section: Discussionmentioning

confidence: 92%

Possible involvement of CD14+ CD16+ monocyte lineage cells in the epidermal damage of Stevens-Johnson syndrome and toxic epidermal necrolysis

Tohyama

Watanabe

Murakami

et al. 2011

British Journal of Dermatology

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Section: Discussionmentioning

confidence: 92%

Possible involvement of CD14+ CD16+ monocyte lineage cells in the epidermal damage of Stevens-Johnson syndrome and toxic epidermal necrolysis

Tohyama

Watanabe

Murakami

et al. 2011

British Journal of Dermatology

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“…There is a growing list of skin diseases associated with apoptosis or with alterations in the regulation of apoptosis in keratinocytes of the epidermis 1 . Apoptosis also plays a pivotal role in GvHD, and enumeration of keratinocyte apoptosis was used recently as an in vitro skin explant assay for GvHD prediction 15 . Further, using this assay Dickinson et al 6 .…”

Section: Discussionmentioning

confidence: 99%

Interferon (IFN)-gamma is a main mediator of keratinocyte (HaCaT) apoptosis and contributes to autocrine IFN-gamma and tumour necrosis factor-alpha production.

et al. 2005

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“…As with the human skin explant assay, it can be used to investigate the role of cytokines (Dickinson et al, 1991; Dickinson et al, 2002; Wang et al, 2002) and innate immunity in GvHR, e.g., heat-shock protein 70 (Jarvis et al, 2002, 2003), the roles of NK cells, dendritic cells (Wilson et al, 2009), regulatory T cells (Wang et al, 2009; Mavin et al, 2012), and subsets of T cells (Dickinson et al, 2002) as well as Fas expression (Ruffin et al, 2011). …”

Section: The Rat Skin Explant Assaymentioning

confidence: 99%

Immune Reconstitution and Graft-Versus-Host Reactions in Rat Models of Allogeneic Hematopoietic Cell Transplantation

Zinöcker¹,

Dressel²,

Wang³

et al. 2012

Front. Immun.

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Allogeneic hematopoietic cell transplantation (alloHCT) extends the lives of thousands of patients who would otherwise succumb to hematopoietic malignancies such as leukemias and lymphomas, aplastic anemia, and disorders of the immune system. In alloHCT, different immune cell types mediate beneficial graft-versus-tumor (GvT) effects, regulate detrimental graft-versus-host disease (GvHD), and are required for protection against infections. Today, the “good” (GvT effector cells and memory cells conferring protection) cannot be easily separated from the “bad” (GvHD-causing cells), and alloHCT remains a hazardous medical modality. The transplantation of hematopoietic stem cells into an immunosuppressed patient creates a delicate environment for the reconstitution of donor blood and immune cells in co-existence with host cells. Immunological reconstitution determines to a large extent the immune status of the allo-transplanted host against infections and the recurrence of cancer, and is critical for long-term protection and survival after clinical alloHCT. Animal models continue to be extremely valuable experimental tools that widen our understanding of, for example, the dynamics of post-transplant hematopoiesis and the complexity of immune reconstitution with multiple ways of interaction between host and donor cells. In this review, we discuss the rat as an experimental model of HCT between allogeneic individuals. We summarize our findings on lymphocyte reconstitution in transplanted rats and illustrate the disease pathology of this particular model. We also introduce the rat skin explant assay, a feasible alternative to in vivo transplantation studies. The skin explant assay can be used to elucidate the biology of graft-versus-host reactions, which are known to have a major impact on immune reconstitution, and to perform genome-wide gene expression studies using controlled combinations of minor and major histocompatibility between the donor and the recipient.

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The detection of apoptosis in a human in vitro skin explant assay for graft versus host reactions

Cited by 29 publications

References 23 publications

Possible involvement of CD14+ CD16+ monocyte lineage cells in the epidermal damage of Stevens-Johnson syndrome and toxic epidermal necrolysis

Possible involvement of CD14+ CD16+ monocyte lineage cells in the epidermal damage of Stevens-Johnson syndrome and toxic epidermal necrolysis

Interferon (IFN)-gamma is a main mediator of keratinocyte (HaCaT) apoptosis and contributes to autocrine IFN-gamma and tumour necrosis factor-alpha production.

Immune Reconstitution and Graft-Versus-Host Reactions in Rat Models of Allogeneic Hematopoietic Cell Transplantation

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