Human peripheral blood CD4 T cell-engrafted non-obese diabetic-scid IL2rγnull H2-Ab1 tm1GruTg (human leucocyte antigen D-related 4) mice: a mouse model of human allogeneic graft-versus-host disease
Year: 2011
Type: article
Abstract: Graft-versus-host disease (GVHD) is a life-threatening complication of human allogeneic haematopoietic stem cell transplantation. Non-obese diabetic (NOD)-scid IL2rγ(null) (NSG) mice injected with human peripheral blood mononuclear cells (PBMC) engraft at high levels and develop a robust xenogeneic (xeno)-GVHD, which reproduces many aspects of the clinical disease. Here we show that enriched and purified human CD4 T cells engraft readily in NSG mice and mediate xeno-GVHD, although with slower kinetics compared to injection of whole PBMC. Moreover, purified human CD4 T cells engraft but do not induce a GVHD in NSG mice that lack murine MHC class II (NSG-H2-Ab1(tm1Gru), NSG-Ab°), demonstrating the importance of murine major histocompatibility complex (MHC) class II in the CD4-mediated xeno-response. Injection of purified human CD4 T cells from a DR4-negative donor into a newly developed NSG mouse strain that expresses human leucocyte antigen D-related 4 (HLA-DR4) but not murine class II (NSG-Ab° DR4) induces an allogeneic GVHD characterized by weight loss, fur loss, infiltration of human cells in skin, lung and liver and a high level of mortality. The ability of human CD4 T cells to mediate an allo-GVHD in NSG-Ab° DR4 mice suggests that this model will be useful to investigate acute allo-GVHD pathogenesis and to evaluate human specific therapies.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Leona M. and Harry B. Helmsley Charitable Trust, National Institutes of Health, Center for AIDS Research, University of Washington, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Molecular Genetics and Mechanisms of Thrombocytopenia, G1205497983, G1483709979, G1649734325, G1778963489, G2677314950, G2999437633, Regulation of Virus-Specific T cell Responses by TNF, Diabetes Endocrinology Research Center (DERC), G5890241971, Viral Infection Influence on Transplantation Tolerance, UMASS Center for AIDS Research (CFAR), Mechanisms of Islet Transplantation Tolerance, Coordinating Center for Beta Cell Biology Consortium, G8810558875, G9000001230, G9000110905, G9000178065, G9000337328, Cancer Center Support (CORE) Grant
OpenAlex ID: W1572378903