Study of Leukemogenesis in Adult T-Cell Leukemia using SCID mouse model

众所周知，HTLV-I是一种致癌的C型逆转录病毒，用于T细胞恶性肿瘤之一，成人T细胞白血病（ATL）。HTLV-Ⅰ是第一个引起人类恶性肿瘤的逆转录病毒。本实验采用免疫球蛋白和T细胞受体基因重排的常染色体隐性突变导致功能性T和B淋巴细胞缺失的scid小鼠作为实验动物模型，通过scid突变小鼠与其他突变小鼠的回交，建立了新的免疫缺陷小鼠。在新的免疫缺陷小鼠品系中重建人T淋巴细胞。用免疫缺陷小鼠建立HTLV-Ⅰ感染系统，用人T细胞淋巴瘤杀死小鼠，免疫缺陷小鼠中的人T细胞淋巴瘤与ATL白血病细胞非常相似，检测到IL-2、IL-10、IFN-γ和M-CSF等细胞因子基因的表达，虽然所有肿瘤细胞都含有完整的HTLV-Ⅰ序列，但tax基因表达较低。这一结果可能暗示tax基因是ATL细胞发育所必需的，而不是维持ATL细胞在体内增殖所必需的。因此，有必要利用免疫缺陷小鼠在体内研究白血病的发生机制。

It is well known that HTLV-I is an oncogenic type C retrovirus for one of the T cell malignancies, adult T-cell leukemia (ATL). HTLV-I is a first human retrovirus which causes the human malignant tumor. Our experiment has been designed to investigate mechanism of leukemogenesis and develop therapy strategy against the ATL using an animal model.In addition of scid mice which have an autosomal recessive mutation of the rearrangement on immunoglobulin and T-cell receptor genes resulting that they lack functional T and B lymphocytes, new immunodeficient mice were developed by either backcrossing of scid mutant onto the other mutant mice. Human T lymphocytes were reconstituted in the new immunodeficient mouse strains. Using the immunodeficient mice we developed the infection system of HTLV-I and the mice were killed by human T-cell lymphoma.The human T-cell lymphoma in the immunodeficient mice was very similar to ATL leukemic cells and we detected active cytokine gene expression such as IL-2, IL-10, IFN-gamma, and M-CSF.Although all tumor cells contained entire HTLV-I sequence, the expression of tax gene was low. This results may implicate that tax gene is required in development of ATL cells and is not essential to maintain the proliferation of the ATL cells in vivo. It is necessary to reveal what kind of factors involve in the leukemogenesis in vivo using the immunodeficient mice.