Chlamydia-specific CD4 T cell clones control Chlamydia muridarum replication in epithelial cells by nitric oxide-dependent and -independent mechanisms.
Chlamydia-specific CD4 T cell clones control Chlamydia muridarum replication in epithelial cells by nitric oxide-dependent and -independent mechanisms.
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DOI：
10.4049/jimmunol.1002596
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Johnson RM
中科院分区：
文献类型：
--
作者：
Jayarapu K;Kerr M;Ofner S;Johnson RM
沙眼衣原体 D-K 血清型是性传播的细胞内细菌病原体，在人类生殖道内壁上皮细胞中复制。从基因敲除小鼠和利用鼠衣原体进行的 T 细胞耗竭研究中可以清楚地看出，MHC II 类和 CD4 T 细胞对于清除小鼠生殖道中的细菌至关重要。目前尚不清楚 CD4 T 细胞如何与感染的上皮细胞相互作用以介导体内细菌清除。先前使用上皮肿瘤细胞系的研究表明，衣原体特异性 CD4 T 细胞克隆能够通过诱导上皮一氧化氮的产生来抑制 C. muridarum 的体外复制。我们之前已经证明，衣原体特异性 CD4 T 细胞克隆可以识别受感染的生殖道上皮细胞并被其激活，并阻止衣原体在其中的复制。我们通过研究一组 CD4 T 细胞克隆控制上皮细胞中衣原体复制的机制来扩展这些观察结果。我们发现衣原体特异性 CD4 T 细胞克隆具有溶细胞作用，但溶细胞作用对于控制鼠衣原体复制可能并不重要。对于一个 CD4 T 细胞克隆诱导的上皮一氧化氮的产生对于控制复制至关重要；然而，最有效的 CD4 T 细胞克隆依赖于 T 细胞脱颗粒来控制复制，一氧化氮的产生仅起到很小的额外作用。我们讨论我们的数据，因为它与现有的敲除小鼠研究有关，这些研究涉及 T 细胞介导的衣原体复制控制机制，及其对小鼠模型中细胞内上皮病原体的影响。
Chlamydia trachomatis serovars D-K are sexually-transmitted intracellular bacterial pathogens that replicate in epithelial cells lining the human reproductive tract. It is clear from knockout mice and T cell depletion studies utilizing Chlamydia muridarum that MHC class II and CD4 T cells are critical for clearing bacteria from the murine genital tract. It is not clear how CD4 T cells interact with infected epithelial cells to mediate bacterial clearance in vivo. Previous work using an epithelial tumor cell line showed that a Chlamydia-specific CD4 T cell clone was able to inhibit C. muridarum replication in vitro via induction of epithelial nitric oxide production. We have previously shown that Chlamydia-specific CD4 T cell clones can recognize and be-activated-by infected reproductive tract epithelial cells, and block Chlamydia replication in them. We extend those observations by investigating the mechanism used by a panel of CD4 T cell clones to control Chlamydia replication in epithelial cells. We found that Chlamydia-specific CD4 T cell clones were cytolytic, but that cytolysis was not likely critical for controlling C. muridarum replication. For one CD4 T cell clone induced epithelial nitric oxide production was critical for controlling replication; however, the most potent CD4 T cell clones were dependent on T cell degranulation for replication control with only a minor additional contribution from nitric oxide production. We discuss our data as it relates to existing knockout mouse studies addressing mechanisms of T cell-mediated control of Chlamydia replication, and their implications for intracellular epithelial pathogens in mouse models.
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DOI：
10.1073/pnas.94.8.3914
发表时间：
1997-04-15
影响因子：
11.1
作者：
Kayagaki, N;Yamaguchi, N;Yagita, H
通讯作者：
Yagita, H
影响因子：
6.4
作者：
Igietseme, JU
通讯作者：
Igietseme, JU
DOI：
10.1016/0002-9378(86)90473-4
发表时间：
1986-04-01
影响因子：
9.8
作者：
KIVIAT, NB;WOLNERHANSSEN, P;HOLMES, KK
通讯作者：
HOLMES, KK
影响因子：
4.8
作者：
Fehlner-Gardiner, C;Roshick, C;McClarty, G
通讯作者：
McClarty, G
影响因子：
3.1
作者：
Derbigny, Wilbert A.;Hong, Soon-Cheol;Johnson, Raymond M.
通讯作者：
Johnson, Raymond M.