Human T-cell lymphotropic/leukemia virus type 1 (HTLV-1) Tax-specific T-cell exhaustion in HTLV-1-infected individuals.
Human T-cell lymphotropic/leukemia virus type 1 (HTLV-1) Tax-specific T-cell exhaustion in HTLV-1-infected individuals.
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DOI：
10.1111/cas.13654
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发表时间：
2018-08
期刊：
影响因子：
5.7
通讯作者：
Iida S
中科院分区：
文献类型：
--
作者：
Masaki A;Ishida T;Suzuki S;Ito A;Narita T;Kinoshita S;Ri M;Kusumoto S;Komatsu H;Inagaki H;Ueda R;Iida S
成人T细胞白血病/淋巴瘤(ATL)是由人类T细胞白血病/白血病病毒1型(HTLV-1)引起的，PBMC中HTLV-1前病毒载量高是ATL发生的危险因素。在这里，我们记录了HTLV-1无症状携带者(AC)和ATL患者的外周血中HTLV-1前病毒载量之间的显著负相关关系(Spearman等级相关系数[Rs]=−0.494，P=0.037，n=0.18)和ATL患者(Rs=−0.774，P=0.001，n=0.15)。HTLV-1前病毒载量与PD-1阳性Tax-CTL的百分比在HTLV-1AC(Rs=0.574，P=0.013)和ATL患者(Rs=0.676，P=0.006)之间也有显著的相关性。此外，PD-1阳性的Tax-CTL的百分率与其功能呈负相关(Rs=−0.542，P=0.020)，与ATL患者的功能呈负相关(Rs=−0.639，P=0.010)。这些发现表明，TAX-CTL的功能随着其程序性细胞死亡蛋白1(PD-1)水平的增加而降低，与PBMC中HTLV-1前病毒载量的增加平行。我们认为，功能的TAX-CTL对于决定HTLV-1前病毒在PBMC中的载量至关重要，不仅在HTLV-1AC中，而且在ATL中也是如此，PD-1的表达水平是TAX-CTL功能的可靠标志。因此，调节TAX-CTL和HTLV-1感染细胞之间的免疫平衡以实现功能效应的优势可能是控制HTLV-1相关疾病的理想策略。
Adult T‐cell leukemia/lymphoma (ATL) is caused by Human T‐cell lymphotropic/leukemia virus type 1 (HTLV‐1), and a higher HTLV‐1 provirus load in PBMC is a risk factor for ATL development. Here, we document a significant inverse correlation between the function of HTLV‐1 Tax‐specific CTL (Tax‐CTL), as assessed by ex vivo cytokine production in response to cognate peptide, and the HTLV‐1 provirus load in PBMC in both HTLV‐1 asymptomatic carriers (AC) (Spearman rank correlation coefficient [Rs] = −0.494, P = .037, n = 18) and ATL patients (Rs = −0.774, P = .001, n = 15). There was also a significant correlation between the HTLV‐1 provirus load and the percentage of PD‐1‐positive Tax‐CTL in both HTLV‐1 AC (Rs = 0.574, P = .013) and ATL patients (Rs = 0.676, P = .006). Furthermore, the percentage of PD‐1‐positive Tax‐CTL was inversely correlated with their function in HTLV‐1 AC (Rs = −0.542, P = .020), and ATL patients (Rs = −0.639, P = .010). These findings indicate that the function of Tax‐CTL decreased as their programmed cell death protein 1 (PD‐1) levels increased, parallel to the increased HTLV‐1 provirus load in PBMC. We propose that functional Tax‐CTL are crucial for determining the HTLV‐1 provirus load in PBMC, not only in HTLV‐1 AC, but also in ATL, and that PD‐1 expression levels are reliable markers of Tax‐CTL function. Thus, modulating the immunological equilibrium between Tax‐CTL and HTLV‐1‐infected cells to achieve dominance of functional effectors could represent an ideal strategy for controlling HTLV‐1‐associated disease.
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无症状 HTLV-1 携带者的人类 T 细胞白血病病毒 I 型（HTLV-1）前病毒载量和疾病进展：日本的一项全国性前瞻性研究
影响因子：
20.3
作者：
Iwanaga, Masako;Watanabe, Toshiki;Yamaguchi, Kazunari
通讯作者：
Yamaguchi, Kazunari
影响因子：
82.9
作者：
Lee, PP;Yee, C;Davis, MM
通讯作者：
Davis, MM
DOI：
10.1038/nri3862
发表时间：
2015-08
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Wherry EJ;Kurachi M
通讯作者：
Kurachi M
DOI：
10.1084/jem.20011723
发表时间：
2002-05-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Reignat S;Webster GJ;Brown D;Ogg GS;King A;Seneviratne SL;Dusheiko G;Williams R;Maini MK;Bertoletti A
通讯作者：
Bertoletti A
影响因子：
5.4
作者：
Radziewicz, Henry;Ibegbu, Chris C.;Grakoui, Arash
通讯作者：
Grakoui, Arash