Stewart S A, Feuer G, Jewett A, Lee F V, Bonavida B, Chen I S
Department of Microbiology & Immunology, University of California at Los Angeles School of Medicine 90095-1747, USA.
Virology. 1996 Dec 15;226(2):167-75. doi: 10.1006/viro.1996.0643.
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL). We have previously shown that the ATL cell line, RV-ATL, formed tumors when inoculated into severe combined immunodeficient (SCID) mice. In contrast, the HTLV-1 in vitro-transformed cell line, SLB-1, was nontumorigenic in SCID mice. ATL cells contain HTLV-1 proviral DNA sequences but lack detectable viral gene expression, in contrast to HTLV-1 in vitro-transformed cells, which express all viral gene products. We investigated the role of HTLV-1 gene expression in tumorigenesis by superinfecting RV-ATL cells with HTLV-1. The resulting cell line, HT-1RV, expressed HTLV-1. Injection of HT-1RV cells into SCID mice resulted in a reduced tumorigenic phenotype compared to the parental RV-ATL cells. In vitro natural killer (NK) cell cytotoxicity assays revealed that cell lines expressing HTLV-1 gene products, SLB-1 and HT-1RV, were sensitive to NK cell cytolysis. In contrast, nonexpressing RV-ATL cells were resistant to NK cell cytolysis. These studies indicate that lack of viral gene expression allows HTLV-1-infected cells to elude detection by murine NK cells and increases tumorigenicity in SCID mice. Thus the loss of HTLV-1 gene expression in ATL cells may be an important mechanism by which leukemic cells escape immune surveillance in humans.
人类T细胞白血病病毒1型（HTLV-1）是成人T细胞白血病（ATL）的病原体。我们之前已经表明，ATL细胞系RV-ATL接种到严重联合免疫缺陷（SCID）小鼠体内时会形成肿瘤。相比之下，HTLV-1体外转化细胞系SLB-1在SCID小鼠中不具有致瘤性。与表达所有病毒基因产物的HTLV-1体外转化细胞不同，ATL细胞含有HTLV-1前病毒DNA序列，但缺乏可检测到的病毒基因表达。我们通过用HTLV-1超感染RV-ATL细胞来研究HTLV-1基因表达在肿瘤发生中的作用。由此产生的细胞系HT-1RV表达HTLV-1。将HT-1RV细胞注射到SCID小鼠体内导致与亲代RV-ATL细胞相比致瘤表型降低。体外自然杀伤（NK）细胞细胞毒性试验表明，表达HTLV-1基因产物的细胞系SLB-1和HT-1RV对NK细胞溶解敏感。相比之下，不表达的RV-ATL细胞对NK细胞溶解具有抗性。这些研究表明，病毒基因表达的缺失使HTLV-1感染的细胞能够逃避小鼠NK细胞的检测，并增加在SCID小鼠中的致瘤性。因此，ATL细胞中HTLV-1基因表达的丧失可能是白血病细胞在人类中逃避免疫监视的重要机制。
