Human T-cell leukemia virus type 2 Tax protein induces interleukin 2-independent growth in a T-cell line
Human T-cell leukemia virus type 2 Tax protein induces interleukin 2-independent growth in a T-cell line
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DOI：
10.1186/1742-4690-3-88
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发表时间：
2006-12-02
期刊：
影响因子：
3.3
通讯作者：
Fujii, Masahiro
中科院分区：
文献类型：
--
作者：
Kondo, Rie;Higuchi, Masaya;Fujii, Masahiro
背景：虽然人类t细胞白血病病毒1型（HTLV-1）是成人t细胞白血病的病原体，但HTLV 2型（HTLV-2）与这种恶性肿瘤无关。越来越多的证据表明，HTLV-1或HTLV-2的转化蛋白Tax在这两种感染的独特发病机制中起着至关重要的作用。我们在小鼠t细胞系CTLL-2中检测了Tax2本身是否具有促生长活性，并与Tax1进行了比较。结果：我们发现Tax2使ctl -2的细胞生长从依赖白细胞介素(IL)-2的生长转变为独立的生长。转录因子NFAT抑制剂环孢素A对4个tax2转化的CTLL-2细胞有2个抑制作用，但对2个tax1转化的CTLL-2细胞影响不大。htlv -2转化的人t细胞系产生大量的IL-2，而tax2转化的ctl -2细胞仅产生极少量的IL-2。这些结果表明，nfat诱导的基因(s)在tax2转化的CTLL-2细胞的生长中起作用，而不是IL-2。结论：这些结果表明HTLV-2 Tax2本身对t细胞系cttl -2具有促生长活性，因此本研究使用的cttl -2检测方法可能是比较t细胞中Tax2与Tax1活性的有用工具，从而阐明HTLV-1特异性白血病发生的机制。
Background: While human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult Tcell leukemia, HTLV type 2 (HTLV-2) is not associated with this malignancy. Accumulating evidence suggests that Tax, a transforming protein of HTLV-1 or HTLV-2, plays a crucial role in the distinctive pathogenesis of these two infections. We herein examined whether Tax2 by itself has a growth promoting activity in a mouse T-cell line CTLL-2, and compared the activity with that of Tax1.Results: We found that Tax2 converts the cell growth of CTLL-2 from an interleukin(IL)-2-dependent growth into an independent one. Cyclosporine A, an inhibitor of transcription factor NFAT, inhibited the growth of two out of four Tax2-transformed CTLL-2 cells, but it had little effect on two Tax1-transformed cells. While the HTLV-2-transformed human T-cell lines produce a significant amount of IL-2, Tax2-transformed CTLL-2 cells only produced a minimal amount of IL-2. These results thus suggest that NFAT-inducible gene(s) other than IL-2 play a role in the cell growth of Tax2-transformed CTLL-2 cells.Conclusion: These results show that HTLV-2 Tax2 by itself has a growth promoting activity toward a T-cell line CTLL-2, and the CTLL-2 assay used in this study may therefore be a useful tool for comparing the activity of Tax2 with that of Tax1 in T-cells, thereby elucidating the mechanism of HTLV-1 specific leukemogenesis.