neoplastic transformation of t lymphocytes through transgenic expression of a virus host modification protein肿瘤的t淋巴细胞通过转基因病毒主机改性蛋白的表达.pdfVIP

Neoplastic Transformation of T Lymphocytes through Transgenic Expression of a Virus Host Modification Protein ´ 1*.¤a 1.¤b ´ 1 2 Sılvia Cristina Paiva Almeida , Vivian Leite de Oliveira , Sonia Ventura , Margarita Bofill , Robert Michael Evans Parkhouse1* ˆ 1 Instituto Gulbenkian de Ciencia, Oeiras, Portugal, 2 Institucio Catalana de Recerca i Estudis Avancats, IrsiCaixa, Barcelona, Spain Abstract Virus host evasion genes are ready-made tools for gene manipulation and therapy. In this work we have assessed the impact in vivo of the evasion gene A238L of the African Swine Fever Virus, a gene which inhibits transcription mediated by both NF-kB and NFAT. The A238L gene has been selectively expressed in mouse T lymphocytes using tissue specific promoter, enhancer and locus control region sequences for CD2. The resulting two independently derived transgenic mice expressed the transgene and developed a metastasic, angiogenic and transplantable CD4+ + – CD8 CD69 lymphoma. The CD4+ + – CD8 CD69 cells also grew vigorously in vitro. The absence of CD69 from the tumour cells suggests that they were derived from T cells at a stage prior to positive selection. In contrast, transgenic mice similarly expressing a mutant A238L, solely inhibiting transcription mediated by NF-kB, were indistinguishable from wild type mice. Expression of Rag1, Rag2, TCR b-V8.2, CD25, FoxP3, Bcl3, Bcl2 l14, Myc, IL-2, NFAT1 and Itk, by purified CD4+ + –