Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression
Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression
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DOI：
10.1182/blood-2010-12-322727
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发表时间：
2011-04-07
期刊：
影响因子：
20.3
通讯作者：
Betts, Michael R.
中科院分区：
文献类型：
--
作者：
Hersperger, Adam R.;Martin, Jeffrey N.;Betts, Michael R.
最近的数据表明，CD8(+) t细胞效应活性是控制精英控制者（ECs）中HIV复制的重要组成部分。CD8(+) t细胞效应因子功能和分化的一个关键因素是T-box转录因子T-bet。在本研究中，我们评估了T-bet以及效应蛋白穿孔蛋白、颗粒酶A（Grz A）、颗粒酶B（Grz B）和颗粒蛋白在ECs （n = 20）、慢性感染进展者（CPs; n = 18）和高活性抗逆转录病毒治疗（HAART）抑制个体（n = 19）的hiv特异性CD8(+) T细胞中的表达。与其他队列组相比，ECs中hiv特异性CD8(+) T细胞表现出更强的表达穿孔素和Grz B的能力，但在Grz a或颗粒蛋白水平上没有可检测到的差异。我们还观察到ECs中hiv特异性CD8(+) T细胞的T-bet水平较高，T-bet与穿孔素和Grz b水平呈正相关。此外，ECs中hiv特异性CD8(+) T细胞在体外扩增后比CPs更大程度地上调T-bet，同时上调穿孔素和Grz b。这些结果表明T-bet可能在驱动效应因子功能中发挥重要作用。它的调节可能会增强对HIV的效应活性。(血。2011;117 (14):3799 - 3808)
Recent data suggest that CD8(+) T-cell effector activity is an important component in the control of HIV replication in elite controllers (ECs). One critical element of CD8(+) T-cell effector function and differentiation is the T-box transcription factor T-bet. In the present study, we assessed T-bet expression, together with the effector proteins perforin, granzyme A(Grz A), granzyme B(Grz B), and granulysin, in HIV-specific CD8(+) T cells from ECs (n = 20), chronically infected progressors (CPs; n = 18), and highly active anti-retroviral therapy (HAART)-suppressed individuals (n = 19). Compared with the other cohort groups, HIV-specific CD8(+) T cells among ECs demonstrated a superior ability to express perforin and Grz B, but with no detectable difference in the levels of Grz A or granulysin. We also observed higher levels of T-bet in HIV-specific CD8(+) T cells from ECs, with an ensuing positive correlation between T-bet and levels of both perforin and Grz B. Moreover, HIV-specific CD8(+) T cells in ECs up-regulated T-bet to a greater extent than CPs after in vitro expansion, with concomitant up-regulation of perforin and Grz B. These results suggest that T-bet may play an important role in driving effector function, and its modulation may lead to enhanced effector activity against HIV. (Blood. 2011;117(14):3799-3808)