Various models of humanized mice have been developed with different genetic manipulations designed to meet the needs of in vivo studies of human systems. Although the current mouse models permit long-term hematopoiesis of human B cells, they do not do well in development of functional human T cells. The current mouse models also fail to develop serum levels of human IgM and IgG comparable to that of human blood. This limitation has been attributed to the lack of expression of human leukocyte antigen (HLA) molecules in mouse lymphoid organs.
Navy researchers have developed a mouse model capable of expressing human leukocyte antigen DR4, and human costimulatory molecules (CD80) upon infusion of human HLA-matched hematopoietic stem cells (HSC), which reconstitute long-lived and functional human T and B cells. One of these models, namely DRAG (HLA-DR4.RagKO.IL2RγcKO.NOD) mice, when infused with HLA II-matched human HSC, develop functional human T and B cells, reconstitute serum levels of all human immunoglobulin classes and subclasses (natural antibodies), and respond to vaccination by eliciting specific antibodies. This mouse model represents a new in vivo model for studies on human T and B cell development and function, vaccine testing, and generation of human IgG monoclonal antibodies for prophylactic or therapeutic use.
- Expression of HLA class II molecules in humanized mice supports the development of a functional human adaptive immune system
- 93 percent of the mice in the study group developed human CD8 T cells (killer T cells)
- Human T cells developed by this mouse model were as functional as those from healthy human volunteers
- US patent 9,557,323 available for license
- Potential for collaboration with Navy researchers