Manipulating the rate of memory CD8+ T cell generation after acute infection
Manipulating the rate of memory CD8+ T cell generation after acute infection
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DOI：
10.4049/jimmunol.179.1.53
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发表时间：
2007-07-01
影响因子：
4.4
通讯作者：
Harty, John T.
中科院分区：
文献类型：
--
作者：
Badovinac, Vladimir P.;Harty, John T.
感染单核细胞增生李斯特菌后，抗原特异性CD 8（+）T细胞数量迅速增加，然后进行程序性收缩。剩余的细胞随着时间的推移经历进一步的表型和功能变化，最终获得记忆CD 8（+）T细胞的品质。在这项研究中，我们表明，L。单核细胞生成素特异性CD 8（+）T细胞群在抗肿瘤预处理的小鼠中引发，经历短暂的效应期，但迅速形成记忆性CD 8（+）T细胞的表型（CD 127（高），CD 43（低））和功能（颗粒酶B-低，IL-2-产生）特征。这些早期记忆性CD 8（+）T细胞能够在感染后第7天对加强攻击做出实质性的二次扩增，导致与对照感染小鼠相比，二次效应和记忆性CD 8（+）T细胞的数量显著增加，保护性免疫增强。虽然早期的扩张在数量上与L.在单核细胞增多症感染的免疫前处理小鼠和对照小鼠中，持续增殖的缺乏加上应答性CD 8（+）T细胞上杀伤细胞凝集素样受体G-1上调的减少可能解释了快速的效应CD 8（+）T细胞向记忆性CD 8（+）T细胞的转变。此外，抗生素治疗后2天L。单核细胞增多症刺激加速了具有记忆表型和功能的CD 8（+）T细胞的产生，并且这种加速的记忆产生在存在CpG诱导的炎症时被逆转。总之，这些数据表明，Ag特异性CD 8（+）T细胞群体在感染后获得记忆特征的速率并不固定，而是可以通过限制炎症来操纵，炎症反过来会调节CD 8（+）T细胞增殖的时间和程度，并上调杀伤细胞凝集素样受体G-1的表达。
Infection with Listeria monocytogenes elicits expansion in numbers of Ag-specific CD8(+) T cells, which then undergo programmed contraction. The remaining cells undergo further phenotypic and functional changes with time, eventually attaining the qualities of memory CD8(+) T cells. In this study, we show that L. monocytogenes-specific CD8(+) T cell populations primed in antibiotic-pretreated mice undergo brief effector phase, but rapidly develop phenotypic (CD127(high), CD43(low))and functional (granzyme B-low, IL-2-producing) characteristics of memory CD8(+) T cells. These early memory CD8(+) T cells were capable of substantial secondary expansion in response to booster challenge at day 7 postinfection, resulting in significantly elevated numbers of secondary effector and memory CD8(+) T cells and enhanced protective immunity compared with control-infected mice. Although early expansion in numbers is similar after L. monocytogenes infection of antibiotic-pretreated and control mice, the absence of sustained proliferation coupled with decreased killer cell lectin-like receptor G-1 up-regulation on responding CD8(+) T cells may explain the rapid effector to memory CD8(+) T cell transition. In addition, antibiotic treatment 2 days post-L. monocytogenes challenge accelerated the generation of CD8(+) T cells with memory phenotype and function, and this accelerated memory generation was reversed in the presence of CpG-induced inflammation. Together, these data show that the rate at which Ag-specific CD8(+) T cell populations acquire memory characteristics after infection is not fixed, but rather can be manipulated by limiting inflammation that will in turn modulate the timing and extent to which CD8(+) T cells proliferate and up-regulate killer cell lectin-like receptor G-1 expression.