TY - JOUR
T1 - 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
AU - Stewart, Sheila A.
AU - Feuer, Gerold
AU - Jewett, Anahid
AU - Lee, Fred V.
AU - Bonavida, Benjamin
AU - Chen, Irvin S.Y.
N1 - Funding Information:
We thank Wendy Aft for preparation of the manuscript and Alexander Black for critical reading of the manuscript. The work was supported by NIH Grant CA38597, the Leukemia Society of America, and the McCarthy Family Foundation. S.S. is supported by Public Health Training Grant GM07185, G.F. is a Special Fellow of the Leukemia Society of America, and I.S.Y.C. was a Scholar of the Leukemia Society of America.
PY - 1996/12/15
Y1 - 1996/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0030589262&partnerID=8YFLogxK
U2 - 10.1006/viro.1996.0643
DO - 10.1006/viro.1996.0643
M3 - Article
C2 - 8955035
AN - SCOPUS:0030589262
VL - 226
SP - 167
EP - 175
JO - Virology
JF - Virology
SN - 0042-6822
IS - 2
ER -