Abstract
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.
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