Serine protease inhibitor 6 is required to protect dendritic cells from the kiss of death.
Serine protease inhibitor 6 is required to protect dendritic cells from the kiss of death.
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DOI：
10.4049/jimmunol.1102667
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发表时间：
2012-02-01
期刊：
影响因子：
--
通讯作者：
Ashton-Rickardt PG
中科院分区：
文献类型：
--
作者：
Lovo E;Zhang M;Wang L;Ashton-Rickardt PG
树突状细胞（DC）如何将抗原呈递给细胞毒性T细胞（CTL）而不通过接触介导的细胞毒性（即所谓的死亡之吻）杀死自己，已被证明是有争议的。利用丝氨酸蛋白酶抑制剂6 （Spi6）缺失的小鼠，我们发现Spi6通过抑制CTL传递的颗粒酶B （GrB）来保护DC免受死亡之吻。用淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染Spi6 KO小鼠，发现CD8α DC存活受损。Spi6 KO CD8α DC的存活受损导致原发性和记忆性lcmv特异性CTL的启动和扩增受损，这可以通过GrB缺乏来纠正。通过消除GrB获得的克隆爆发恢复表明，GrB是Spi6保护DC免受CTL侵害的生理靶点。我们得出结论，通过CTL杀伤对DC启动CD8 T淋巴细胞免疫的负调控可以通过Spi6对GrB的生理抑制而减轻。
How dendritic cells (DC) present antigen to cytotoxic T cells (CTL) without themselves being killed through contact mediated cytotoxicity (so called kiss of death) has proven to be controversial. Using mice deficient in Serine Protease Inhibitor 6 (Spi6) we show that Spi6 protects DC from the kiss of death by inhibiting granzyme B (GrB) delivered by CTL. Infection of Spi6 KO mice with Lymphocytic Choriomeningits virus (LCMV) revealed impaired survival of CD8α DC. The impaired survival of Spi6 KO CD8α DC resulted in impaired priming and expansion of both primary and memory LCMV-specific CTL, which could be corrected by GrB deficiency. The rescue in the clonal burst obtained by GrB elimination demonstrated that GrB was the physiological target through which Spi6 protected DC from CTL. We conclude that the negative regulation of DC priming of CD8 T lymphocyte immunity by CTL killing is mitigated by the physiological inhibition of GrB by Spi6.
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影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
DOI：
10.1084/jem.20031799
发表时间：
2004-04-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Wolint P;Betts MR;Koup RA;Oxenius A
通讯作者：
Oxenius A
影响因子：
64.8
作者：
LAU, LL;JAMIESON, BD;AHMED, R
通讯作者：
AHMED, R
影响因子：
4.1
作者：
Annand, RR;Dahlen, JR;Giegel, DA
通讯作者：
Giegel, DA
影响因子：
32.4
作者：
Cao, Xuefang;Cai, Sheng F.;Ley, Timothy J.
通讯作者：
Ley, Timothy J.