The survival of memory CD8 T cells that is mediated by IL-15 correlates with sustained protection against malaria.
The survival of memory CD8 T cells that is mediated by IL-15 correlates with sustained protection against malaria.
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DOI：
10.4049/jimmunol.1203396
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发表时间：
2013-05-15
期刊：
影响因子：
--
通讯作者：
Krzych U
中科院分区：
文献类型：
--
作者：
Zarling S;Berenzon D;Dalai S;Liepinsh D;Steers N;Krzych U
感染或疫苗接种引起的ag特异性记忆T细胞反应与持久的保护性免疫密不可分。对疟疾流行地区居民保护性免疫的研究表明，对疟原虫抗原的记忆反应没有充分发展或维持，因为童年疟疾发作后幸存下来的人仍然容易受到持续或间歇性疟疾感染。相比之下，多次暴露于辐射减弱的疟原虫孢子（γ-spz）可诱导对实验性孢子虫的持久保护性免疫。我们之前已经证明，伯氏疟原虫(Pb) γ-spz诱导的无菌保护是mhc - i类依赖的，CD8 T细胞是关键的效应细胞。在Pb γ-spz免疫的B6小鼠中出现的IFN-γ+CD8 T细胞主要存在于肝脏中，对肝期Ag储备水平敏感，它们表达CD44hiCD62Llo标记物，指示效应/效应记忆（E/EM）表型。发育相关的中央记忆（CM） CD8 T细胞表达CD122 （IL-15Rβ）水平升高，这表明CD8 TCM细胞依赖IL-15来维持。使用IL-15缺陷小鼠，我们在这里证明，尽管保护性免疫在这些小鼠中是可诱导的，但保护是短暂的，主要是由于CD8 TCM细胞无法在IL-15缺陷环境中存活。我们提出了一个与模型一致的假设，即肝内CD8 TCM细胞由il -15介导的存活和基础增殖维持，在随后的感染中被招募到CD8 TE/EM细胞池中。
Ag-specific memory T cell responses elicited by infections or vaccinations are inextricably linked to long-lasting protective immunity. Studies of protective immunity amongst residents of malaria endemic areas indicate that memory responses to Plasmodia antigens are not adequately developed or maintained, as persons who survive episodes of childhood malaria are still vulnerable to either persistent or intermittent malaria infections. In contrast, multiple exposures to radiation-attenuated Plasmodia sporozoites (γ-spz) induce long-lasting protective immunity to experimental sporozoite challenge. We previously demonstrated that sterile protection induced by Plasmodium berghei (Pb) γ-spz is MHC-class I-dependent and CD8 T cells are the key effectors. IFN-γ+CD8 T cells that arise in Pb γ-spz immunized B6 mice are found predominantly in the liver and are sensitive to levels of liver-stage Ag depot and they express CD44hiCD62Llo markers indicative of effector/effector memory (E/EM) phenotype. The developmentally related central memory (CM) CD8 T cells express elevated levels of CD122 (IL-15Rβ), which suggests that CD8 TCM cells depend upon IL-15 for maintenance. Using IL-15 deficient mice, we demonstrate here that although protective immunity is inducible in these mice, protection is short-lived, mainly owing to the inability of CD8 TCM cells to survive in the IL-15 deficient milieu. We present a hypothesis consistent with a model whereby intrahepatic CD8 TCM cells, being maintained by IL-15-mediated survival and basal proliferation, are conscripted into CD8 TE/EM cell pool during subsequent infections.
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DOI：
10.1084/jem.20052237
发表时间：
2006-04-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jabbari A;Harty JT
通讯作者：
Harty JT
影响因子：
15.3
作者：
Goldrath, Ananda W;Sivakumar, Pallavur V;Glaccum, Moira;Kennedy, Mary K;Bevan, Michael J;Benoist, Christophe;Mathis, Diane;Butz, Eric A
通讯作者：
Butz, Eric A
影响因子：
6.7
作者：
Cockburn IA;Chen YC;Overstreet MG;Lees JR;van Rooijen N;Farber DL;Zavala F
通讯作者：
Zavala F
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R
DOI：
10.4269/ajtmh.1993.49.166
发表时间：
1993-08-01
影响因子：
3.3
作者：
EGAN, JE;HOFFMAN, SL;GORDON, DM
通讯作者：
GORDON, DM