Xenotransplantation of human cells into immunodeficient mice has been used to develop models of human hematopoiesis and immune function. In this study, we generated the NOD/Scid mice with null mutation of Jak-3 (NOD/Scid/Jak-3 null) by 10 backcross mating of C57/BL6-Jak-3 null mice and NOD/Scid mice. NOD/Scid/Jak-3 null mice had NK and NKT cells as well as mature T and B lymphocytes. NK activity was not also detected in this mice.

Intrahepatic injection of CD34+ human cord blood cells into irradiated (2.0Gy) newborn NOD/Scid/Jak-3 null mice led to de novo development of B and T lymphocytes. In addition to the high engraftment rate of human hematopoietic cells, multilineage cell differentiation including T cell lineage was obserbed. T lymphocyte appeared in peripheral blood as early as 8 weeks after transplantation and it was increased in number thereafter. Both naive and memory phenotype CD4 and CD8 T lymphocytes were detected 12 weeks after transplantation. Plasma cells were detected in the bone marrow 20 weeks after transplantation.

Furthermore the engrafted mice were infected with HIV. Our model mice provide a valuable model to study not only development and function of human hematopoeitic and immune system but also the immune response to the cancer and infectious disease such as HIV.

Topics:
engraftment, mice, knockout, severe combined immunodeficiency, t-cell development, transplantation, cancer, communicable diseases, hiv infections, immunologic deficiency syndromes, transplantation, heterologous

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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