HTLV-I gene expression in adult T-cell leukemia cells elicits an NK cell response in vitro and correlates with cell rejection in SCID mice

Sheila A. Stewart, Gerold Feuer, Anahid Jewett, Fred V. Lee, Benjamin Bonavida, Irvin S.Y. Chen

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Human T-cell leukemia virus type I (HTLV-I) 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-I in vitro-transformed cell line, SLB-I, was nontumorigenic in SCID mice. ATL cells contain HTLV-I proviral DNA sequences but lack detectable viral gene expression, in contrast to HTLV-I in vitro-transformed cells, which express all viral gene products. We investigated the role of HTLV-I gene expression in tumorigenesis by superinfecting RV-ATL cells with HTLV-I. The resulting cell line, HT-1RV, expressed HTLV-I. 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-I gene products, SLB-I 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-I-infected cells to elude detection by murine NK cells and increases tumorigenicity in SCID mice. Thus the loss of HTLV-I gene expression in ATL cells may be an important mechanism by which leukemic cells escape immune surveillance in humans.

Original languageEnglish
Pages (from-to)167-175
Number of pages9
JournalVirology
Volume226
Issue number2
DOIs
StatePublished - Dec 15 1996

Fingerprint

Dive into the research topics of 'HTLV-I gene expression in adult T-cell leukemia cells elicits an NK cell response in vitro and correlates with cell rejection in SCID mice'. Together they form a unique fingerprint.

Cite this