Early Signals during CD8+ T Cell Priming Regulate the Generation of Central Memory Cells
Early Signals during CD8+ T Cell Priming Regulate the Generation of Central Memory Cells
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DOI：
10.4049/jimmunol.1000492
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发表时间：
2010-07-01
影响因子：
4.4
通讯作者：
Lefrancois, Leo
中科院分区：
文献类型：
--
作者：
Obar, Joshua J.;Lefrancois, Leo
CD 8（+）T细胞对感染的应答的特征在于短寿命（CD 127（低）杀伤细胞凝集素样受体G1-高）和记忆前体（CD 127（高）杀伤细胞凝集素样受体G1-低）效应细胞的出现。中枢记忆T（T-CM; CD 62 L（高）CCR 7（+））细胞和效应记忆T（T-EM; CD 62 L（低）CCR 7（-））细胞亚群是如何以及何时建立的尚不清楚。我们现在表明，TCM细胞谱系代表了CD 8（+）T细胞对感染反应的早期发育分支点。中央记忆性CD 8（+）T细胞可在CD 8（+）T细胞反应达到峰值之前被识别，并在淋巴器官中富集。此外，T-CM细胞发育的动力学和大小取决于感染因子。此外，调节程序性死亡-1和CD 25表达水平的早期Ag可用性的程度最终通过IL-2和IL-15信号传导水平控制T-CM/T-EM细胞谱系决定。这些观察确定了有助于建立T-CM/T-EM细胞二分法的关键早期信号，并提供了操纵记忆谱系选择的方法。免疫学杂志，2010，185：263-272。
The CD8(+) T cell response to infection is characterized by the appearance of short-lived (CD127(low) killer cell lectin-like receptor G 1-high) and memory-precursor (CD127(high) killer cell lectin-like receptor G 1-low) effector cells. How and when central-memory T (T-CM; CD62L(high) CCR7(+)) cell and effector-memory T(T-EM; CD62L(low) CCR7(-)) cell subsets are established remains unclear. We now show that the TCM cell lineage represents an early developmental branchpoint during the CD8(+) T cell response to infection. Central-memory CD8(+) T cells could be identified prior to the peak of the CD8(+) T cell response and were enriched in lymphoid organs. Moreover, the kinetics and magnitude of T-CM cell development were dependent on the infectious agent. Furthermore, the extent of early Ag availability, which regulated programmed death-1 and CD25 expression levels, controlled the T-CM/T-EM cell lineage decision ultimately through IL-2 and IL-15 signaling levels. These observations identify key early signals that help establish the T-CM/T-EM cell dichotomy and provide the means to manipulate memory lineage choices. The Journal of Immunology, 2010, 185: 263-272.