Infection of human natural killer (NK) cells with replication-defective human T cell leukemia virus type I provirus. Increased proliferative capacity and prolonged survival of functionally competent NK cells.
Human T-cell leukemia virus type I (HTLV-I) can infect a variety of human cell types, but only T lymphocytes are efficiently immortalized after HTLV-I infection. This study reports an attempt to infect and to immortalize NK cells with HTLV-I. Co-cultivation of freshly isolated NK cells with a HTLV-I-producing T cell line did not result in NK cell infection. However, NK cells activated with an anti-CD16 mAb and co-cultivated with a HTLV-I-producing T cell line were reproducibly infected by HTLV-I. HTLV-I infection was documented in NK cell lines and clones by the detection of defective integrated provirus by both Southern blot and polymerase chain reaction analysis. Although HTLV-I-infected NK cells produced viral proteins, they did not produce infectious viral particles. HTLV-I-infected NK cells were phenotypically indistinguishable from their uninfected counterparts (CD16+, CD2+, CD56+, CD3-). They also retained the ability to mediate both natural and antibody-dependent cell cytotoxicity. The IL-2-dependent proliferation of HTLV-I-infected NK cells was significantly greater than that of uninfected NK cells. The doubling time of this infected population was reduced from 9 days to 3 days, and the overall survival of the culture in the absence of restimulation was extended from 5 wk to 18 wk. Unlike T lymphocytes, HTLV-I-infected NK cells were not immortal, implying a fundamental difference between these two lymphocyte populations.
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Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, MA 02115.
Vivier
E
E
Rochet
N
N
Dehni
G
G
Levine
H
H
Haseltine
W A
WA
Anderson
P
P
D001483:Base Sequence; D015153:Blotting, Western; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000032:analysis; D005434:Flow Cytometry; D005814:Genes, Viral; D015490:HTLV-I Infections / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000382:microbiology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D017452:Receptors, IgG / Q000502:physiology
D016692:Receptors, Antigen, T-Cell, gamma-delta; D017452:Receptors, IgG; D004247:DNA