CRTAM Confers Late-Stage Activation of CD8+ T Cells to Regulate Retention within Lymph Node
CRTAM Confers Late-Stage Activation of CD8+ T Cells to Regulate Retention within Lymph Node
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DOI：
10.4049/jimmunol.0901248
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发表时间：
2009-10-01
影响因子：
4.4
通讯作者：
Saito, Takashi
中科院分区：
文献类型：
--
作者：
Takeuchi, Arata;Itoh, Yasushi;Saito, Takashi
在体内，免疫反应是在淋巴结中触发的，淋巴细胞进入、滞留和迁移到效应部位是动态调节的。滞留调节的分子机制是阐明体内免疫应答调节的关键。在这项研究中，我们描述了黏附分子I类限制性T细胞相关分子(CRTAM)在调节CD8(+)T细胞在淋巴结内的滞留以及最终的效应功能中的作用。我们以前发现CRTAM是一种受体，主要表达在活化的CD8(+)T细胞上，Necl2是它的配体。通过建立CRTAM(-/-)小鼠，分析CRTAM-Necl2相互作用的体内功能。在体内，CRTAM(-/-)小鼠对病毒感染和自身免疫性糖尿病诱导的保护性免疫降低。尽管抗原特异性CRTAM(-/-)CD8(+)T细胞在体外表现出正常的CTL功能，但其在引流淋巴结中的数量减少。由于CRTAM(+)T细胞与位于淋巴结T细胞区的表达Necl2的CD8(+)树突状细胞(DC)有效结合，CRTAM可能通过与CD8(+)树突状细胞(DC)结合在增殖前的活化后期而诱导CD8(+)DC滞留。CRTAM介导的晚期与DC的相互作用诱导活化的CD8(+)T细胞以不依赖于抗原的方式滞留，这可能导致引流淋巴结中有效的CTL发展。免疫学杂志，2009,183：4220-4228。
In vivo immune response is triggered in the lymph node, where lymphocytes for entry into, retention at, and migration to effector sites are dynamically regulated. The molecular mechanism underlying retention regulation is the key to elucidating in vivo regulation of immune response. In this study, we describe the function of the adhesion molecule class I-restricted T cell-associated molecule (CRTAM) in regulating CD8(+) T cell retention within the lymph node and eventually effector function. We previously identified CRTAM as a receptor predominantly expressed on activated CD8(+) T cells, and nectin-like molecule-2 (Necl2) as its ligand. In vivo function of CRTAM-Necl2 interaction was analyzed by generating CRTAM(-/-) mice. CRTAM(-/-) mice exhibited reduced protective immunity against viral infection and impaired autoimmune diabetes induction in vivo. Although Ag-specific CRTAM(-/-) CD8(+) T cells showed normal CTL functions in vitro, their number in the draining lymph node was reduced. Because CRTAM(+) T cells bound efficiently to Necl2-expressing CD8(+) dendritic cells (DCs) that reside in T cell area of lymph node, CRTAM may induce retention by binding to CD8(+) DCs at the late stage of activation before proliferation. The CRTAM-mediated late interaction with DCs induced retention of activated CD8(+) T cells in an Ag-independent fashion, and this possibly resulted in effective CTL development in the draining lymph node. The Journal of Immunology, 2009, 183: 4220-4228.