Broad Recognition of Circulating HIV-1 by HIV-1-Specific Cytotoxic T-Lymphocytes with Strong Ability to Suppress HIV-1 Replication
Broad Recognition of Circulating HIV-1 by HIV-1-Specific Cytotoxic T-Lymphocytes with Strong Ability to Suppress HIV-1 Replication
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具有强大抑制 HIV-1 复制能力的 HIV-1 特异性细胞毒性 T 淋巴细胞对循环 HIV-1 的广泛识别
DOI：
10.1128/jvi.01480-18
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发表时间：
2019
影响因子：
5.4
通讯作者：
Takiguchi M (* equal contribution)
中科院分区：
文献类型：
--
作者：
Murakoshi H*;Kuse N*;Akahoshi T;Zhang Y;Chikata T;Borghan MA;Gatanaga H;Oka S;Sakai K;Takiguchi M (* equal contribution)
HIV-1特异性细胞毒性T淋巴细胞（CTL）具有很强的抑制HIV-1复制和识别HIV-1流行毒株的能力，是治疗和预防艾滋病疫苗的效应T细胞候选者。先前的研究表明，在日本，11个表位特异性CTL的存在与良好的临床结局显著相关，尽管这些表位之一特异性CTL选择逃逸突变。然而，对其余10个表位特异的CTL是否在体外抑制HIV-1的复制并识别循环中的HIV-1仍不清楚。在这里，我们研究了这些CTL抑制HIV-1复制和识别循环HIV-1变体的能力。对10个表位有特异性的CTL克隆在体外具有较强的抑制HIV-1复制的能力。T细胞对变异表位肽的反应的体外和体外分析表明，对10个表位特异的T细胞识别在84.1%至98.8%的日本HIV-1感染者中发现的HIV-1流行株中检测到的突变肽。此外，对5个表位具有特异性的T细胞很好地识别了感染有7种突变病毒的靶细胞，这些突变病毒在>5%的测试个体中被检测到。综上所述，这些结果表明，特异性的10个表位的CTL有效地抑制HIV-1复制，并广泛地识别HIV-1感染者中的循环HIV-1毒株。这项研究表明，这些T细胞在临床试验中的使用。重要在最近的T细胞艾滋病疫苗试验中，疫苗并没有防止HIV-1感染，虽然HIV-1特异性T细胞在接种疫苗的个人诱导，这表明T细胞有一个弱的能力，抑制HIV-1复制，并不能识别循环HIV-1。我们先前证明了对10个表位的T细胞应答与良好的临床结果显著相关。然而，没有直接证据表明这些T细胞具有强大的抑制HIV-1复制和识别循环HIV-1的能力。在这里，我们证明了对10个表位特异的T细胞在体外具有很强的抑制HIV-1复制的能力。此外，T细胞交叉识别HIV-1感染者中的大部分循环HIV-1。这项研究表明，在T细胞疫苗的临床试验中使用对这10个表位具有特异性的T细胞作为治愈治疗。
HIV-1-specific cytotoxic T-lymphocytes (CTLs) with strong abilities to suppress HIV-1 replication and recognize most circulating HIV-1 strains are candidates for effector T cells for cure treatment and prophylactic AIDS vaccine. Previous studies demonstrated that the existence of CTLs specific for 11 epitopes was significantly associated with good clinical outcomes in Japan, although CTLs specific for one of these epitopes select for escape mutations. However, it remains unknown whether the CTLs specific for the remaining 10 epitopes suppress HIV-1 replicationin vitroand recognize circulating HIV-1. Here, we investigated the abilities of these CTLs to suppress HIV-1 replication and to recognize variants in circulating HIV-1. CTL clones specific for 10 epitopes had strong abilities to suppress HIV-1 replicationin vitro. Theex vivoandin vitroanalyses of T-cell responses to variant epitope peptides showed that the T cells specific for 10 epitopes recognized mutant peptides which are detected in 84.1% to 98.8% of the circulating HIV-1 strains found in HIV-1-infected Japanese individuals. In addition, the T cells specific for 5 epitopes well recognized target cells infected with 7 mutant viruses that had been detected in >5% of tested individuals. Taken together, these results suggest that CTLs specific for the 10 epitopes effectively suppress HIV-1 replication and broadly recognize the circulating HIV-1 strains in the HIV-1-infected individuals. This study suggests the use of these T cells in clinical trials.IMPORTANCEIn recent T-cell AIDS vaccine trials, the vaccines did not prevent HIV-1 infection, although HIV-1-specific T cells were induced in the vaccinated individuals, suggesting that the T cells have a weak ability to suppress HIV-1 replication and fail to recognize circulating HIV-1. We previously demonstrated that the T-cell responses to 10 epitopes were significantly associated with good clinical outcome. However, there is no direct evidence that these T cells have strong abilities to suppress HIV-1 replication and recognize circulating HIV-1. Here, we demonstrated that the T cells specific for the 10 epitopes had strong abilities to suppress HIV-1 replicationin vitro. Moreover, the T cells cross-recognized most of the circulating HIV-1 in HIV-1-infected individuals. This study suggests the use of T cells specific for these 10 epitopes in clinical trials of T-cell vaccines as a cure treatment.
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影响因子：
30.3
作者：
Marsden MD;Zack JA
通讯作者：
Zack JA
HIV 特异性颗粒酶 B 分泌而非γ干扰素分泌 T 细胞与早期 HIV 感染中病毒库减少相关
影响因子：
5.4
作者：
F. Yue;J. Cohen;M. Ho;A. Rahman;Jun Liu;S. Mujib;A. Saiyed;Sabrina Hundal;Alexandra Khozin;P. Bonner;Daheng Liu;E. Benko;C. Kovacs;Mario A. Ostrowski;Mario A. Ostrowski
通讯作者：
Mario A. Ostrowski
影响因子：
3.2
作者：
Rajalingam, R;Krausa, P;Parham, P
通讯作者：
Parham, P
影响因子：
5.4
作者：
Kawashima, Yuka;Kuse, Nozomi;Takiguchi, Masafumi
通讯作者：
Takiguchi, Masafumi
影响因子：
4.4
作者：
Hoof, Ilka;Perez, Carina L.;Karlsson, Annika C.
通讯作者：
Karlsson, Annika C.