Expression of the target antigen for cytotoxic T lymphocytes on adult T-cell-leukemia cells.
Adult T-cell-leukemia (ATL) cells were examined for susceptibility to human T-cell-leukemia virus type I (HTLV-I) tax-specific cytotoxic T lymphocytes (CTL) derived from a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). These CTL efficiently killed HLA-matched leukemia cells of an ATL patient after overnight incubation. However, ATL cells immediately after isolation from the peripheral blood were only marginally susceptible to the CTL. This is not due to inappropriate expression of major-histocompatibility-complex (MHC)-class-I antigen on the leukemia cells. Addition of synthetic peptide, corresponding to the CTL epitope, to the assay enabled the CTL to kill the fresh ATL cells. Scarcity of HTLV-I antigens in the fresh ATL cells and induction of these antigens by in vitro incubation were demonstrated both on the cell surface and in the cytoplasm. Lectin stimulation augmented synthesis of HTLV-I antigens, but was not essential for the induction. The presence in the culture of human plasma containing a high titer of antibodies to HTLV-I did not affect the induction of HTLV-I expression in the ATL cells. Furthermore, significantly lower levels of HTLV-I tax mRNA were present in the fresh ATL cells than in the cultured ATL cells, whereas the levels of HTLV-I proviral tax gene did not differ among these cells. This suppression of HTLV-I transcription in fresh ATL cells accounts for resistance to the CTL, and could be a reason for the persistence of HTLV-I infection in vivo.
Department of Biodefence and Medical Virology, Kumamoto University School of Medicine, Japan.
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Kannagi
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Matsushita
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Harada
D000368:Aged; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D016356:Gene Products, tax / Q000276:immunology*; D015486:HTLV-I Antigens / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000502:physiology; D006801:Humans; D015458:Leukemia, T-Cell / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication
D004279:DNA, Viral; D016356:Gene Products, tax; D015486:HTLV-I Antigens; D012367:RNA, Viral