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Humanized Mice Show Promise for the Study of Xenogeneic Graft-Versus-Host Reactions

Apr 24, 2017 4:39:47 PM / by Stacy Matthews Branch, DVM, PhD

Scientists developed a humanized mouse model to study the immunological reactions to human PBMCs.Research into the prevention or amelioration of graft-versus-host disease is a priority in the transplantation arena. The use of mouse models help in understanding the mechanisms and efficacy of proposed approaches to this issue. For example, the application of regulatory T cells is one area of investigation using mouse models treated with human peripheral blood mononuclear cells (PBMCs). However, the current mouse models limit the interpretation for its potential use in humans because the immune reactions observed are only to the mouse cells.

To address this dilemma, scientists developed a humanized mouse model to study the immunological reactions to human PBMCs. That is, the mice were developed to express human immune-related molecules, human leukocyte antigen (HLA, specifically HLA-A*0201) and human 2 microglobulin (a component of HLA class I molecules). These mice and non-humanized control  mice were transplanted with either HLA-A2+ or HLA-A2− human PBMCs obtained from healthy donors. Differences in survival, degree of graft-versus-host reaction, platelet levels (representing hematopoiesis), and immune cell levels in various organs were compared between the humanized and non-humanized mice.

Survival rates were lower in the humanized mice, and they had more severe graft-versus-host reactions. There was a larger difference in the survival time between the two mouse types transplanted with HLAA2− PBMCs when compared to those transplanted with HLAA2+. There was also a stronger adverse effect on hematopoiesis (given the lower platelet counts) in the humanized mice. For the organs studied (blood, bone marrow, liver, spleen, lungs), there were higher levels of cytotoxic T cells, and the ratio of T helper cells to cytotoxic T cells were lower in those from humanized mice.

One interpretation may be that the differences were due to higher proliferation of the cytotoxic T cells, but the scientists ruled that out because they saw no differences between the mouse types in KI67 (a marker of cell proliferation). These results suggest that the higher cytotoxic T cell levels reflect the immune reaction to the human HLA-A2 antigen. Therefore, these humanized mice may represent a viable option to study the prevention and treatment of graft-versus-host disease in humans.

At HemaCare, we offer high quality, customizable peripheral blood mononuclear cells for your biomedical studies.  To make a purchase or to learn more about our products, visit us online or call us at 877-397-3087 today.

Ehx, Grégory et al. "Comparison Of Xenogeneic Graft-Versus-Host Reactions In Humanized NSG And NSG-HLA-A2/HHD Mice". N.p., 2017. Web. 19 Apr. 2017.

Topics: bioresearch, PBMCs, Basic Research

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