1. 3080 – HUMANIZED DRAGA MOUSE MODEL RECAPITULATES HUMAN T-CELL DIFFERENTIATION IN THE MOUSE THYMUS WITH HLA-MATCHED DONORS.
- Author
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Gonzalez, Laura, Wang, Fangwu, MacAldaz, Margarita, Wu, Vivian, Lau, Yasmine Yuen Man, Wang, Keheng, Knapp, David, Zandstra, Peter, and Eaves, Connie
- Subjects
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HUMAN biology , *CORD blood , *IMMUNE checkpoint inhibitors , *MAJOR histocompatibility complex , *B cells - Abstract
Differences between mice and humans, such as variations in the major histocompatibility complex (MHC) and variances in immune system function, pose challenges to accurately model human biology in mice. Therefore, improving humanized mouse models, particularly models of human hematopoietic lineages (such as functional lymphocytes), is essential. This optimization is especially relevant to the study of the immune system for advancing treatments like CAR-T therapy and immune checkpoint inhibitors in cancer treatment. A novel mouse model with the essential immune components needed to generate mature B and T cells has been developed. The DRAGA mouse model has an NRG background and carries human HLA-A2 and HLA-DR4 transgenes. These transgenes have been shown to enhance hematopoietic engraftment and promote the development of fully functional T cells and antibody-secreting B cells (Casares, 2016). To test the ability of the DRAGA mouse strain to support the late-stage differentiation of human B- and T-cells from HLA-matched cord blood (CB) progenitors, we transplanted 10,000 matched or unmatched CD34+ CB cells into DRAGA mice. We then tracked the output of human hematopoietic cells for 20 weeks. Analysis showed higher T- and B-cell progenitors in the bone marrow of mice engrafted with matched cord blood progenitors compared to unmatched ones, indicating that HLA compatibility may enhance mature T-cell selection and early lymphopoiesis. In addition, comparing matched cord blood progeny with infant human thymus tissue reveals similar T-lineage phenotypes, suggesting this model replicates this aspect of human T cell development and maturation in mice. Our findings suggest that the DRAGA mouse holds promise as a model for creating a humanized immune system. This model may be valuable for studying immunotherapies and exploring immune cell functions across different cancer types. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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