Kannagi M, Matsushita S, Harada S
Department of Biodefence and Medical Virology, Kumamoto University School of Medicine, Japan.
Int J Cancer. 1993 Jun 19;54(4):582-8. doi: 10.1002/ijc.2910540411.
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.
对成人T细胞白血病（ATL）细胞进行检测，以确定其对源自一名患有人T细胞白血病病毒I型（HTLV-I）相关脊髓病/热带痉挛性截瘫（HAM/TSP）患者的HTLV-I tax特异性细胞毒性T淋巴细胞（CTL）的敏感性。这些CTL在过夜培养后能有效杀伤一名ATL患者的HLA匹配的白血病细胞。然而，刚从外周血中分离出的ATL细胞对CTL的敏感性仅为边缘性。这并非由于白血病细胞上主要组织相容性复合体（MHC）I类抗原表达不当所致。在检测中加入与CTL表位对应的合成肽，可使CTL杀伤新鲜的ATL细胞。新鲜ATL细胞中HTLV-I抗原稀少，且在体外培养时这些抗原在细胞表面和细胞质中均有诱导产生。凝集素刺激可增强HTLV-I抗原的合成，但对诱导并非必需。含有高滴度抗HTLV-I抗体的人血浆存在于培养物中，并不影响ATL细胞中HTLV-I表达的诱导。此外，新鲜ATL细胞中HTLV-I tax mRNA的水平明显低于培养的ATL细胞，而这些细胞中HTLV-I前病毒tax基因的水平并无差异。新鲜ATL细胞中HTLV-I转录的这种抑制解释了其对CTL的抗性，并且可能是HTLV-I在体内持续感染的一个原因。
