Potential immunogenicity of adult T cell leukemia cells in vivo
Potential immunogenicity of adult T cell leukemia cells in vivo
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DOI：
10.1002/ijc.20737
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发表时间：
2005-03-20
影响因子：
6.4
通讯作者：
Kannagi, M
中科院分区：
文献类型：
--
作者：
Kurihara, K;Harashima, N;Kannagi, M
针对人T细胞白血病病毒I型（HTLV-I）Tax的实验性疫苗已在HTLV-I诱导的淋巴瘤大鼠模型中得到证实。然而，HTLV-I表达的缺乏和成人T细胞白血病（ATL）细胞中缺陷HTLV-I-前病毒的存在引起了关于HTLV-I靶向免疫疗法在人类中的治疗潜力的争议。我们研究了HTLV-I抗原在新鲜ATL细胞中的表达，通过使用体外和体内测定。在流式细胞术分析中，我们发现5名急性型ATL患者中的3名和15名慢性型ATL患者中的6名在1天培养中在他们的ATL细胞中显示出HTLV-1 Tax和Gag的显著诱导。伴随着HTLV-I表达，这些ATL细胞表达共刺激分子，如CD 80，CD 86和OX 40，并显示出对同种异体T细胞和HTLV-I Tax特异性细胞毒性T淋巴细胞（CTL）的抗原性水平升高。受HLA-A2或A24限制的代表性CTL表位在5例急性型ATL患者中的4例中是保守的。此外，皮下接种福尔马林固定的未培养ATL细胞的大鼠脾T细胞显示出对HTLV-1 Tax表达细胞特异性的强的产生干扰素γ的辅助T细胞应答。我们的研究表明，大约一半的患者的ATL细胞容易表达HTLV-I抗原，包括Tax在体外，ATL细胞表达足够量的Tax或Tax诱导的抗原，在体内引起特异性T细胞反应。(C)2004 Wiley-Liss，Inc.
Experimental vaccines targeting human T cell leukemia virus type-I (HTLV-I) Tax have been demonstrated in a rat model of HTLV-I-induced Iymphomas. However, the scarcity of HTLV-I-expression and the presence of defective HTLV-I-proviruses in adult T cell leukemia (ATL) cells have raised controversy about the therapeutic potential of HTLV-I-targeted immunotherapy in humans. We investigated the expression of HTLV-I antigens in fresh ATL cells by using both in vitro and in vivo assays. In flow cytometric analysis, we found that 3 of 5 acute-type and six of fifteen chronic-type ATL patients tested showed significant induction of HTLV-I Tax and Gag in their ATL cells in a 1-day culture. Concomitantly with HTLV-I-expression, these ATL cells expressed co-stimulatory molecules such as CD80, CD86 and OX40, and showed elevated levels of antigenicity against allogeneic T cells and HTLV-I Tax-specific cytotoxic T-lymphocytes (CTL). Representative CTL epitopes restricted by HLA-A2 or A24 were conserved in 4 of 5 acute-type ATL patients tested. Furthermore, spleen T cells from rats, which had been subcutaneously inoculated with formalin-fixed uncultured ATL cells, exhibited a strong interferon gamma-producing helper T cell responses specific for HTLV-I Tax-expressing cells. Our study indicated that ATL cells from about half the patients tested readily express HTLV-I antigens including Tax in vitro, and that ATL cells express sufficient amounts of Tax or Tax-induced antigens to evoke specific T cell responses in vivo. (C) 2004 Wiley-Liss, Inc.