TLR2 Engagement on CD8 T Cells Enables Generation of Functional Memory Cells in Response to a Suboptimal TCR Signal
TLR2 Engagement on CD8 T Cells Enables Generation of Functional Memory Cells in Response to a Suboptimal TCR Signal
复制标题
DOI：
10.4049/jimmunol.0801167
复制
发表时间：
2009-02-15
影响因子：
4.4
通讯作者：
Bonnefoy-Berard, Nathalie
中科院分区：
文献类型：
--
作者：
Mercier, Blandine C.;Cottalorda, Anne;Bonnefoy-Berard, Nathalie
TLR参与检测微生物感染以及哺乳动物中发出组织和细胞损伤信号的内源性配体。这种识别在先天免疫应答和适应性免疫应答的启动中起着重要作用。我们以前已经表明，鼠CD 8 T细胞表达TLR 2，并与TLR 2配体的Ag激活的CD 8 T细胞的共刺激增强其增殖，存活和效应功能。我们还证明了CD 8 T细胞上的TLR 2参与显著降低了它们对APC递送的共刺激信号的需求。我们在这项研究中表明，CD 8 T细胞上的TLR 2参与降低了最佳活化所需的Ag浓度，并将部分活化转化为生产过程，导致细胞的显著扩增。使用改变的肽配体，我们证明了TLR 2参与增加了CD 8 T细胞活化，并能够响应低TCR信号产生功能性记忆细胞。这种增加的激活与PI 3 K的增强激活相关。综上所述，我们的结果表明，CD 8 T细胞上的TLR 2接合降低了它们对TCR信号强度的激活阈值，并且能够响应于弱TCR信号而有效地产生记忆细胞。免疫学杂志，2009，182：1860-1867。
TLR are involved in the detection of microbial infection as well as endogenous ligands that signal tissue and cell damage in mammals. This recognition plays an essential role in innate immune response and the initiation of adaptive immune response. We have previously shown that murine CD8 T cells express TLR2, and that costimulation of Ag-activated CD8 T cells with TLR2 ligands enhances their proliferation, survival, and effector functions. We also demonstrated that TLR2 engagement on CD8 T cells significantly reduces their need for costimulatory signals delivered by APC. We show in this study that TLR2 engagement on CD8 T cells lowers the Ag concentration required for optimal activation, and converts a partial activation into a productive process leading to a significant expansion of cells. Using altered peptide ligands, we demonstrate that TLR2 engagement increases CD8 T cell activation and enables the generation of functional memory cells in response to a low TCR signal. This increased activation is associated with an augmented activation of the PI3K. Taken together, our results demonstrate that TLR2 engagement on CD8 T cells lowers their activation threshold for TCR signal strength and enables efficient memory cell generation in response to a weak TCR signal. The Journal of Immunology, 2009, 182: 1860-1867.