Modelling Graft-Versus-Host Disease in Mice Using Human Peripheral Blood Mononuclear Cells
Manjurul Haque,
Dominic Boardman,
Avery Lam,
Katerine MacDonald,
Lieke Sanderink,
Qing Huang,
Vivian Fung,
Sabine Ivison,
Majid Mojibian,
Megan Levings
Affiliations
Manjurul Haque
Department of Surgery, The University of British Columbia, Vancouver BC, CanadaBC Children’s Hospital Research Institute, Vancouver BC, Canada
Dominic Boardman
Department of Surgery, The University of British Columbia, Vancouver BC, CanadaBC Children’s Hospital Research Institute, Vancouver BC, Canada
Avery Lam
Department of Surgery, The University of British Columbia, Vancouver BC, CanadaBC Children’s Hospital Research Institute, Vancouver BC, Canada
Katerine MacDonald
BC Children’s Hospital Research Institute, Vancouver BC, CanadaSchool of Biomedical Engineering, The University of British Columbia, Vancouver BC, Canada
Lieke Sanderink
Department of Surgery, The University of British Columbia, Vancouver BC, CanadaBC Children’s Hospital Research Institute, Vancouver BC, Canada
Qing Huang
Department of Surgery, The University of British Columbia, Vancouver BC, CanadaBC Children’s Hospital Research Institute, Vancouver BC, Canada
Vivian Fung
Department of Surgery, The University of British Columbia, Vancouver BC, CanadaBC Children’s Hospital Research Institute, Vancouver BC, Canada
Sabine Ivison
Department of Surgery, The University of British Columbia, Vancouver BC, CanadaBC Children’s Hospital Research Institute, Vancouver BC, Canada
Majid Mojibian
Department of Surgery, The University of British Columbia, Vancouver BC, CanadaBC Children’s Hospital Research Institute, Vancouver BC, Canada
Megan Levings
Department of Surgery, The University of British Columbia, Vancouver BC, CanadaBC Children’s Hospital Research Institute, Vancouver BC, Canada, School of Biomedical Engineering, The University of British Columbia, Vancouver BC, Canada
Graft-versus-host disease (GvHD) is a significant complication of allogeneic hematopoietic stem cell transplantation. In order to develop new therapeutic approaches, there is a need to recapitulate GvHD effects in pre-clinical, in vivo systems, such as mouse and humanized mouse models. In humanized mouse models of GvHD, mice are reconstituted with human immune cells, which become activated by xenogeneic (xeno) stimuli, causing a multi-system disorder known as xenoGvHD. Testing the ability of new therapies to prevent or delay the development of xenoGvHD is often used as pre-clinical, proof-of-concept data, creating the need for standardized methodology to induce, monitor, and report xenoGvHD. Here, we describe detailed methods for how to induce xenoGvHD by injecting human peripheral blood mononuclear cells into immunodeficient NOD SCID gamma mice. We provide comprehensive details on methods for human T cell preparation and injection, mouse monitoring, data collection, interpretation, and reporting. Additionally, we provide an example of the potential utility of the xenoGvHD model to assess the biological activity of a regulatory T-cell therapy. Use of this protocol will allow better standardization of this model and comparison of datasets across different studies.Graphical abstract
