Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I-associated neuroimmunological disease.
Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I-associated neuroimmunological disease.
复制标题
DOI：
10.1172/jci23913
复制
发表时间：
2005-05
期刊：
影响因子：
--
通讯作者：
Y. Yamano;N. Takenouchi;Hong-Chuan Li;U. Tomaru;Karen Yao;C. Grant;D. Marić;S. Jacobson
中科院分区：
文献类型：
--
作者：
Y. Yamano;N. Takenouchi;Hong-Chuan Li;U. Tomaru;Karen Yao;C. Grant;D. Marić;S. Jacobson
CD4(+)CD25(+)Tregs在维持自身免疫耐受和预防自身免疫性疾病中具有重要作用。由于人类T细胞淋巴组织病毒I型相关性脊髓病/热带痉挛麻痹(HAM/TSP)患者的CD4(+)CD25(+)T细胞群已被证明是该病毒的主要宿主，因此确定HAM/TSP患者的CD4(+)CD25(+)Tregs的频率和功能是否可能受到影响是有意义的。在这些细胞中，Tregs的特异性标志物叉头转录因子Foxp3的mRNA和蛋白表达均低于健康人的CD4(+)CD25(+)T细胞。病毒编码的反式激活HTLV-I Tax基因对CD4(+)CD25(+)T细胞的Foxp3表达和功能有直接抑制作用。这是我们所知的第一个关于特定病毒基因产物(HTLV-I Tax)在Tregs相关基因(特别是Foxp3)表达上的作用，从而抑制Treg功能的报道。这些结果提示人类对CD4(+)CD25(+)T细胞的直接逆转录病毒感染可能与HTLV-I相关神经系统疾病的发病机制有关。
CD4(+)CD25(+) Tregs are important in the maintenance of immunological self tolerance and in the prevention of autoimmune diseases. As the CD4(+)CD25(+) T cell population in patients with human T cell lymphotropic virus type I-associated (HTLV-I-associated) myelopathy/tropical spastic paraparesis (HAM/TSP) has been shown to be a major reservoir for this virus, it was of interest to determine whether the frequency and function of CD4(+)CD25(+) Tregs in HAM/TSP patients might be affected. In these cells, both mRNA and protein expression of the forkhead transcription factor Foxp3, a specific marker of Tregs, were lower than those in CD4(+)CD25(+) T cells from healthy individuals. The virus-encoded transactivating HTLV-I tax gene was demonstrated to have a direct inhibitory effect on Foxp3 expression and function of CD4(+)CD25(+) T cells. This is the first report to our knowledge demonstrating the role of a specific viral gene product (HTLV-I Tax) on the expression of genes associated with Tregs (in particular, foxp3) resulting in inhibition of Treg function. These results suggest that direct human retroviral infection of CD4(+)CD25(+) T cells may be associated with the pathogenesis of HTLV-I-associated neurologic disease.