Distinct roles of cytolytic effector molecules for antigen-restricted killing by CTL in vivo.
Distinct roles of cytolytic effector molecules for antigen-restricted killing by CTL in vivo.
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DOI：
10.1038/icb.2010.37
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发表时间：
2010-10
影响因子：
4
通讯作者：
Pinkoski, Michael J.
中科院分区：
文献类型：
--
作者：
Janssen, Edith M.;Lemmens, Ed E.;Gour, Naina;Reboulet, Rachel A.;Green, Douglas R.;Schoenberger, Stephen P.;Pinkoski, Michael J.
细胞毒性 T 淋巴细胞 (CTL) 是免疫系统的前线防御之一，可杀死病毒感染的细胞和肿瘤转化的细胞。 CTL 使用至少两种机制诱导其靶标发生细胞凋亡，一种由穿孔素和颗粒酶介导，另一种由死亡配体 CD95 配体 (CD95L) 触发。在这里，我们使用体内细胞毒性测定来测量先前用非感染性细胞相关抗原免疫的小鼠中携带抗原的靶细胞的特异性清除率。我们发现，穿孔素对于有效清除免疫小鼠中的抗原携带细胞来说是可有可无的，但前提是 CD95/CD95L 具有功能；然而，在没有穿孔素的情况下，靶细胞清除会出现延迟。此外，我们观察到在不存在穿孔素和CD95L的情况下大约35%的靶细胞清除率，而在存在中和性抗TNF抗体的情况下仅略微消除该清除率。显性失活 Fas 相关死亡结构域 (FADD) 的存在不会阻碍靶细胞清除，因此不能归因于已知的死亡受体。总而言之，这些数据表明，穿孔素和 CD95L 依赖性杀伤在早期时间点是互补的，可以在后期时间点各自补偿对方的缺失，并且抗原限制性 CTL 杀伤存在独立于穿孔素、CD95L 和 TNFα 的附加成分。
Cytotoxic T lymphocytes (CTL) represent one of the front lines of defense for the immune system, killing virus-infected and tumor-transformed cells. CTL use at least two mechanisms to induce apoptosis in their targets, one mediated by perforin and granzymes, and the other triggered by the death ligand, CD95-ligand (CD95L). Here we used an in vivo cytotoxicity assay to measure specific clearance of antigen-bearing target cells in mice that had previously been immunized with non-infectious cell-associated-antigens. We found that perforin was dispensable for efficient clearance of antigen-bearing cells from immunized mice, but only if CD95/CD95L was functional; however, there was a delay in target cell clearance in the absence of perforin. Additionally, we observed approximately 35% target cell clearance in the absence of both perforin and CD95L which was only slightly abrogated in the presence of a neutralizing anti-TNF antibody. The presence of a dominant negative Fas-Associated Death Domain (FADD) did not block target cell clearance and therefore cannot be attributed to known death receptors. Taken together these data suggest that perforin- and CD95L-dependent killing are complementary at early time points, can each compensate for the absence of the other at later time points and that there is an additional component of antigen-restricted CTL killing independent of both perforin, CD95L and TNFα.
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影响因子：
64.8
作者：
BELLGRAU, D;GOLD, D;DUKE, RC
通讯作者：
DUKE, RC
影响因子：
5.4
作者：
ISAAZ, S;BAETZ, K;GRIFFITHS, GM
通讯作者：
GRIFFITHS, GM
影响因子：
4.4
作者：
Barber, DL;Wherry, EJ;Ahmed, R
通讯作者：
Ahmed, R
DOI：
10.1073/pnas.262660999
发表时间：
2002-12-10
影响因子：
11.1
作者：
Pinkoski, MJ;Droin, NM;Green, DR
通讯作者：
Green, DR
影响因子：
32.4
作者：
Griffith, TS;Yu, XH;Ferguson, TA
通讯作者：
Ferguson, TA