Abstract: |
A HLA-DR1 transgenic mouse (NOD/scid-DR1) was derived by breeding the existing B10.M/J-[Tg]DR1 mouse with the NOD/scid mouse. The intention was to enhance engraftment of human T cells by providing human class II elements in the tissues. Thymus and spleen fragments from adult NOD/scid-DR1 mice were transplanted under the syngeneic kidney capsules, followed by injection of human cord blood mononuclear cells (CBMNC) into transplanted tissues. FACS analyses showed that human T and B cells were consistently detected in the peripheral blood and spleen, of the chimeric mice. An average of 20% of human cells was found in the spleen and the engrafted thymus/spleen tissues. Furthermore, human cells from these tissues could proliferate with anti-human CD3 antibody and these mice could generate humoral and cellular responses to allogeneic human cells. Cytokines, such as IL-10, GMCSF, IFN-γ, and TNF-α were also detected in the supernatants of the cultured human cells from the chimeric mice, when they were stimulated with allogeneic cells. Therefore, a novel mouse model with functional circulating human T and B cells was established that would facilitate the exploration of vaccine, the disease processes of autoimmunity, HIV infection, and human cancer. © 2005 Elsevier Inc. All rights reserved. |
Keywords: |
controlled study; allograft; human cell; nonhuman; cd3 antigen; lymphocyte proliferation; t-lymphocytes; mouse; animals; mice; spleen; granulocyte macrophage colony stimulating factor; interleukin 10; animal experiment; cell differentiation; mice, scid; transgenic mouse; mus musculus; mice, transgenic; chimera; cellular immunity; tumor necrosis factor alpha; mononuclear cell; leukocytes, mononuclear; gamma interferon; thymus gland; transplantation, heterologous; adoptive transfer; cytokine production; graft survival; mouse strain; mice, inbred nod; humoral immunity; fluorescence activated cell sorting; t lymphocyte activation; scid mouse; transplantation chimera; antibody production; kidney capsule; thymus graft; umbilical cord; b lymphocyte activation; lymphocyte culture; humans; human; male; female; priority journal; article; dr1 transgenic nod/scid mice; scid-hu mice; hla dr1 antigen; spleen transplantation; hla-dr1 antigen
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