HTLV-1 gene expression in adult T-cell leukemia cells elicits an NK cell response in vitro and correlates with cell rejection in SCID mice.
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.
Stewart
S A
SA
Department of Microbiology & Immunology, University of California at Los Angeles School of Medicine 90095-1747, USA.
Feuer
G
G
Jewett
A
A
Lee
F V
FV
Bonavida
B
B
Chen
I S
IS
D000818:Animals; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D005814:Genes, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015458:Leukemia, T-Cell / Q000276:immunology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009368:Neoplasm Transplantation