CD8-positive Lymphocytes in Graft-Versus-Host Disease of Humanized NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ Mice

Abstract

Immunocompromised mice that can support a human immune system are an increasingly important model for the investigation of haemopoietic stem/progenitor cell (HSPC) development and human infectious disease. NOD-SCID IL-2Rγ(-/-) (NSG) mice engrafted with human fetal liver and thymus prior to HSPC engraftment, commonly known as NSG-bone marrow-liver-thymus (NSG-hu-BLT) mice, are one such model and have robust reconstitution of human leucocytes within the peripheral blood and tissues. Four NSG-hu-BLT mice were submitted for diagnostic necropsy examination following the development of alopecia, pruritus and lethargy after HSPC engraftment. Histopathology revealed multifocal to coalescing single keratinocyte cell death in the epidermis and follicles with dermatitis and mild dermal fibrosis. Single-cell hepatocyte cell death was present in three cases, with various degrees of portal fibrosis. In the skin and liver, cell death was associated with lymphocytes that reacted with anti-human CD45, CD3 and CD8 antibodies, consistent with a diagnosis of graft-versus-host disease (GvHD). This study expands on recently reported microscopical features of GvHD in NSG-hu-BLT mice and suggests a role for CD8(+) T lymphocytes in the progression of the disease. NSG-hu-BLT mice represent an excellent model of GvHD, but its prevalence may compromise their use in other fields of biomedical research.