The dissection of CD8 T cells during liver-stage infection.

The dissection of CD8 T cells during liver-stage infection.
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肝脏阶段感染期间 CD8 T 细胞的解剖。

DOI:
10.1007/3-540-29967-x_1
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发表时间:
2005
影响因子:
--
通讯作者:
J. Schwenk
J. Schwenk
中科院分区:
医学3区
文献类型:
--
作者:
U. Krzych;J. Schwenk

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多次注射γ-辐射减毒疟原虫子孢子(γ-spz)可以诱导针对疟疾红细胞前期阶段的长寿命无菌免疫。产生IFN-γ的疟疾抗原(Ag)特异性CD 8 T细胞是这种保护模型中的关键效应细胞。尽管有许多关于脾脏中γ-spz诱导的CD 8 T细胞的报道,但CD 8 T细胞最有可能通过靶向受感染的肝细胞来提供保护。因此,在本章中,我们讨论的意见和假设有关的CD 8 T细胞反应发生在肝脏后,遇到疟原虫寄生虫。针对红细胞前期阶段的预防性保护需要记忆性CD 8 T细胞,我们讨论了γ-spz诱导的免疫确实伴随着肝内CD 44 hi CD 45 RBlo CD 62 lo CD 122 lo效应记忆(EM)CD 8 T细胞和CD 44 hi CD 45 RBhi CD 621 hi CD 122 hi中央记忆(CM)CD 8 T细胞的存在的证据。此外,EM CD 8 T细胞响应于spz攻击而快速释放IFN-γ。还考虑了枯否细胞在spz Ags加工和细胞因子产生中的可能作用。最后,我们讨论的证据是一致的模型,其中肝内CM CD 8 T细胞维持IL-15介导的稳态增殖,而EM CD 8 T细胞被征召从CM池在响应一个持久的仓库的肝脏阶段Ag。
Multiple injections of gamma-radiation-attenuated Plasmodium sporozoites (gamma-spz) can induce long-lived, sterile immunity against pre-erythrocytic stages of malaria. Malaria antigen (Ag)-specific CD8 T cells that produce IFN-gamma are key effector cells in this model of protection. Although there have been numerous reports dealing with gamma-spz-induced CD8 T cells in the spleen, CD8 T cells most likely confer protection by targeting infected hepatocytes. Consequently, in this chapter we discuss observations and hypotheses concerning CD8 T cell responses that occur in the liver after an encounter with the Plasmodium parasite. Protracted protection against pre-erythrocytic stages requires memory CD8 T cells and we discuss evidence that gamma-spz-induced immunity is indeed accompanied by the presence of intrahepatic CD44hi CD45RBlo CD62lo CD122lo effector memory (EM) CD8 T cells and CD44hi CD45RBhi CD621hi CD122hi central memory (CM) CD8 T cells. In addition, the EM CD8 T cells rapidly release IFN-gamma in response to spz challenge. The possible role of Kupffer cells in the processing of spz Ags and the production of cytokines is also considered. Finally, we discuss evidence that is consistent with a model whereby intrahepatic CM CD8 T cells are maintained by IL-15 mediated-homeostatic proliferation while the EM CD8 T cells are conscripted from the CM pool in response to a persisting depot of liver-stage Ag.
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