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A new xenograft model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2-/- γc-/- double-mutant mice
Abstract
The safe application of new strategies for the treatment of graft-versus-host disease (GVHD) is hampered by the lack of a clinically relevant model for preclinical testing. Current models are based on intraperitoneal transfer of human peripheral blood mononuclear cells (huPBMCs) into NOD-SCID (nonobese diabetic-severe combined immunodeficient)/SCID mice. Intravenous transfer would be preferred but this has always been ineffective. We developed a new model for xenogeneic GVHD (X-GVHD) by intravenous transfer of huPBMCs into RAG2-/- γc-/-mice. Our results show a high human T-cell chimerism of more than 20% (up to 98%) in more than 90% of mice, associated with a consistent development of XGVHD within 14 to 28 days and a total mortality rate of 85% shorter than 2 months. After murine macrophage depletion, engraftment was earlier and equally high with lower doses of huPBMCs. Human macrophages were also absent in these mice. Purified huCD3+ cells showed a similar X-GVH effect with contribution of both CD4 and CD8 phenotypes. Human immunoglobulins and cytokines were produced in diseased mice. One of 30 mice developed chronic X-GVHD with skin histology similar to human GVHD. In conclusion, we present a new model for X-GVHD by intravenous transfer of huPBMCs in RAG2-/- γc-/- mice. Murine and human macrophages do not seem to be necessary for acute X-GVHD in this model. (Blood. 2003;102:2522-2531)
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Cited by
Tumor Regression and Delayed Onset Toxicity Following B7-H4 CAR T Cell Therapy
Smith, J. B., Lanitis, E., Dangaj, D., Buza, E., Poussin, M., Stashwick, C., Scholler, N., & Powell, D. J. (2016) · Molecular Therapy · doi:10.1038/mt.2016.149 · Cited by 58
“Induction of xenogeneic GVHD phenotypes can be highly variable across cohorts of mice, but commonly effect skin [46-48], liver [46-50], gastrointestinal tract [46, 47], and the lung [46, 48-50].”
Human allograft rejection in humanized mice: a historical perspective
Brehm, M. A., & Shultz, L. D. (2012) · Cellular & Molecular Immunology · doi:10.1038/cmi.2011.64 · Cited by 30
Metadata
- Authors
- van Rijn, R. S., Simonetti, E. R., Hagenbeek, A., Hogenes, M. C. H., de Weger, R. A., Canninga-van Dijk, M. R., Weijer, K., Spits, H., Storm, G., van Bloois, L., Rijkers, G., Martens, A. C. M., & Ebeling, S. B.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-10-01
- Volume
- 102
- Issue
- 7
- Pages
- 2522-2531
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2120028488
- Cited by
- 185
- References
- 0
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: A new xenograft model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2-/- γc-/- double-mutant mice. https://app.cochat.ai/papers/10.1182/blood-2002-10-3241
- The paper
- van Rijn, R. S., Simonetti, E. R., Hagenbeek, A., Hogenes, M. C. H., de Weger, R. A., Canninga-van Dijk, M. R., Weijer, K., Spits, H., Storm, G., van Bloois, L., Rijkers, G., Martens, A. C. M., & Ebeling, S. B. (2003). A new xenograft model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2-/- γc-/- double-mutant mice. Blood. https://doi.org/10.1182/blood-2002-10-3241
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
