Читать книгу The Peripheral T-Cell Lymphomas - Группа авторов - Страница 84

Several lines of transgenic mice expressing Tax under the control of viral promoters HTLV1 long terminal repeat have been developed. These mice develop mesenchymal tumors [30], arthritis [31], and osteoporosis [32]. Mesenchymal tumors were observed in the nose, ear, foot, and tail and were characterized by a spindle‐cell component and granulocyte infiltration. However, these models do not mimic human ATLL. Other investigators generated Tax transgenic mice using promoters activated in T cells [33, 34]. Among these, transgenic mice expressing Tax from the Cd3‐epsilon promoter developed a variety of tumors dependent on the lines, including mesenchymal tumors, and salivary and mammary adenomas [33]. Transgenic mice expressing Tax in thymocytes under control of the Lck proximal promoter developed thymic T‐cell lymphomas [34]. Moreover, the other transgenic mice expressing Tax using the GrzmB promoter developed large granular lymphocytic leukemia, lymphadenopathy, extranodal disease and hypercalcemia, resembling human ATLL [35, 36].

Transgenic mice expressing HBZ have also been developed [37, 38]. Mice expressing HBZ driven by the Cd4 promoter showed inflammatory lesions of lung and skin, accompanied by increase of effector/memory and regulatory CD4⁺ T cells [37]. Approximately 40% of these mice also develop T‐cell lymphomas after a long latency, reminiscent of human ATL. HBZ transgenic mice constructed using the GrzmB promoter were also reported [38] and exhibited lymphoproliferative disease, osteoporosis, splenomegaly, and hypercalcemia, similar to lymphoma‐type of ATLL. HBZ/Tax double transgenic mice in which both genes were controlled by the Cd4 promoter showed phenotypes similar to those of HBZ single transgenic mice [39]. Despite this progress, to date a model fully replicating human ATLL disease has not yet been established likely due to the complexity of the human ATLL disease.