Akimoto Masaki, Kozako Tomohiro, Sawada Takashi, Matsushita Kakushi, Ozaki Atsuo, Hamada Heiichiro, Kawada Hideaki, Yoshimitsu Makoto, Tokunaga Masahito, Haraguchi Koichi, Uozumi Kimiharu, Arima Naomichi, Tei Chuwa
Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.
J Med Virol. 2007 Jul;79(7):977-86. doi: 10.1002/jmv.20807.
Previous studies have suggested that higher anti-human T-lymphotropic virus 1 (HTLV-1) antibody titer and lower anti-HTLV-1 Tax antibody reactivity are risk factors for adult T-cell leukemia/lymphoma. In the present study, we analyzed the relationships between these factors and clarified their significance. Forty-five carriers were examined for anti-HTLV-1 and anti-Tax antibody by ELISA. In addition, 43 of the 45 carriers with HLA-A0201 and/or A2402 were examined for frequency of Tax-specific cytotoxic T lymphocytes (CTLs) using HTLV-1/HLA tetramers, and 44 were examined for proviral load by real-time PCR. The relationships between these factors were analyzed statistically. The frequencies of Tax11-19 and Tax301-309-specific CTLs were significantly higher in the anti-Tax antibody-positive group as compared with the antibody-negative group (P = 0.002 and 0.033, respectively). Anti-HTLV-1 antibody titer had a positive correlation with proviral load (P = 0.019), whereas anti-Tax antibody did not show a significant correlation. Higher frequencies of both Tax11-19 and Tax301-309-specific CTLs are related to a reduction in proviral load (P = 0.017 and 0.015, respectively). Synergistic interactions of humoral and cellular immunity against Tax protein were demonstrated in HTLV-1 carriers. Tax-specific CTL may reduce HTLV-1 proviral load to prevent asymptomatic carriers from developing adult T-cell leukemia/lymphoma.
以往研究表明，抗人类嗜T淋巴细胞病毒1型（HTLV-1）抗体滴度较高和抗HTLV-1 Tax抗体反应性较低是成人T细胞白血病/淋巴瘤的危险因素。在本研究中，我们分析了这些因素之间的关系并阐明了它们的意义。通过酶联免疫吸附测定法（ELISA）对45名携带者检测抗HTLV-1和抗Tax抗体。此外，对45名携带HLA-A0201和/或A2402的携带者中的43名，使用HTLV-1/HLA四聚体检测Tax特异性细胞毒性T淋巴细胞（CTL）的频率，对44名携带者通过实时聚合酶链反应（PCR）检测前病毒载量。对这些因素之间的关系进行了统计学分析。与抗体阴性组相比，抗Tax抗体阳性组中Tax11-19和Tax301-309特异性CTL的频率显著更高（P分别为0.002和0.033）。抗HTLV-1抗体滴度与前病毒载量呈正相关（P = 0.019），而抗Tax抗体未显示出显著相关性。Tax11-19和Tax301-309特异性CTL的较高频率均与前病毒载量的降低有关（P分别为0.017和0.015）。在HTLV-1携带者中证实了针对Tax蛋白的体液免疫和细胞免疫的协同相互作用。Tax特异性CTL可能会降低HTLV-1前病毒载量，以防止无症状携带者发展为成人T细胞白血病/淋巴瘤。
