In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity.
In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity.
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DOI：
10.1016/j.immuni.2016.01.010
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发表时间：
2016-02-16
期刊：
影响因子：
32.4
通讯作者：
Förster R
中科院分区：
文献类型：
--
作者：
Halle S;Keyser KA;Stahl FR;Busche A;Marquardt A;Zheng X;Galla M;Heissmeyer V;Heller K;Boelter J;Wagner K;Bischoff Y;Martens R;Braun A;Werth K;Uvarovskii A;Kempf H;Meyer-Hermann M;Arens R;Kremer M;Sutter G;Messerle M;Förster R
根据体外试验，T 细胞被认为能够快速有效地杀死病毒，但细胞毒性 T 淋巴细胞 (CTL) 介导的体内病毒感染细胞杀伤作用的功效和动态仍然难以捉摸。我们使用双光子显微镜来量化感染疱疹病毒或痘病毒的小鼠中 CTL 介导的杀伤作用。根据实时成像和数学模型确定，平均而言，一个 CTL 每天杀死 2-16 个病毒感染的细胞。相比之下，在病毒诱导 MHC I 类下调时，CTL 未能破坏其靶标。在杀伤过程中，CTL 保持迁移并与目标形成活动激酶而不是静态突触。编码钙传感器 GCaMP6s 的病毒在个体 CTL 功能能力方面表现出强烈的异质性。此外，对于那些与两个以上 CTL 接触的细胞，感染细胞死亡的可能性增加，表明 CTL 合作。因此，在杀死病毒感染细胞的过程中直接观察 CTL 可以揭示 CD8+ T 细胞免疫的关键参数。双光子成像表明 CTL 每天杀死 2-16 个病毒感染的细胞 CTL 在杀死病毒感染的细胞时形成激酶而不是稳定的突触 一些 CTL 接触会在病毒感染的细胞中触发持久的钙通量 CTL 在杀死病毒感染的细胞过程中可以合作 根据体外测定，T 细胞被认为能够快速有效地杀死病毒。 Forster 及其同事使用双光子显微镜发现，体内单个细胞毒性 T 淋巴细胞 (CTL) 的杀伤能力是异质且有限的。当多个 CTL 攻击病毒感染的细胞时，靶细胞死亡概率的量化确定了有效的协同杀伤。
According to in vitro assays, T cells are thought to kill rapidly and efficiently, but the efficacy and dynamics of cytotoxic T lymphocyte (CTL)-mediated killing of virus-infected cells in vivo remains elusive. We used two-photon microscopy to quantify CTL-mediated killing in mice infected with herpesviruses or poxviruses. On average, one CTL killed 2–16 virus-infected cells per day as determined by real-time imaging and by mathematical modeling. In contrast, upon virus-induced MHC class I downmodulation, CTLs failed to destroy their targets. During killing, CTLs remained migratory and formed motile kinapses rather than static synapses with targets. Viruses encoding the calcium sensor GCaMP6s revealed strong heterogeneity in individual CTL functional capacity. Furthermore, the probability of death of infected cells increased for those contacted by more than two CTLs, indicative of CTL cooperation. Thus, direct visualization of CTLs during killing of virus-infected cells reveals crucial parameters of CD8+ T cell immunity. Two-photon imaging indicates that CTLs kill 2–16 virus-infected cells per day CTLs form kinapses rather than stable synapses when killing virus-infected cells Some CTL contacts trigger long-lasting calcium fluxes in virus-infected cells CTLs can cooperate during killing of virus-infected cells According to in vitro assays, T cells are thought to kill rapidly and efficiently. Using two-photon microscopy, Forster and colleagues have found that killing capacities of single cytotoxic T lymphocytes (CTLs) in vivo are heterogeneous and limited. Quantification of target-cell-death probabilities identified efficient cooperative killing when multiple CTLs attacked a virus-infected cell.