Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor
Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor
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DOI：
10.1182/blood-2005-04-1684
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发表时间：
2006-02-15
期刊：
影响因子：
20.3
通讯作者：
Shibuya, A
中科院分区：
文献类型：
--
作者：
Tahara-Hanaoka, S;Shibuya, K;Shibuya, A
脊髓灰质炎病毒受体CD155及其家族成员CD112 （nectin-2）是CD8(+) T细胞和自然杀伤（NK）细胞上激活细胞表面受体DNAM-1的配体。在这里，我们证明，虽然RMA肿瘤在同基因小鼠中生长，但DNAM-1配体转导的RMA被排斥，其中CD8(+) T细胞和NK细胞发挥了重要作用。重要的是，在这些小鼠中产生了CD8（+）记忆细胞毒T细胞。我们发现DNAM-1也在CD8 α(+)而不是CD8 α(-)树突状细胞（dc）上表达。交联DNAM-1诱导CD8 α (+) dc成熟。这些受刺激的dc的抗原呈递驱动Th1细胞。此外，在CD4(+) t细胞缺失和主要组织相容性复合物ii类缺陷小鼠中，DNAM-1配体转导的RMA的排斥反应被取消。综上所述，这些结果表明，DNAM-1配体通过CD8 α (+) dc和NK细胞刺激先天免疫，从而有效地启动细胞介导的肿瘤特异性免疫。[血液。2006;107:1491-1496](c) 2006年由美国血液学会出版。
The poliovirus receptor CD155 and its family member CD112 (nectin-2) are the ligands for the activating cell-surface receptor DNAM-1 on CD8(+) T cells and natural killer (NK) cells. Here, we demonstrate that, whereas the RMA tumor grew in syngeneic mice, DNAM-1 ligand-transduced RMA was rejected, in which CD8(+) T cells and NK cells played an essential role. Importantly, CD8(+) memory cytotoxic T cells to parental RMA were generated in these mice. We found that DNAM-1 was also expressed on CD8 alpha(+), rather than CD8 alpha(-), dendritic cells (DCs). Cross-linking DNAM-1 induced maturation of CD8 alpha(+) DCs. Antigen presentation by these stimulated DCs drove Th1 cells. Moreover, the rejection of DNAM-1 ligand-transduced RMA was canceled in CD4(+) T-cell-depleted and major histocompatibility complex class II-deficient mice. Taken together, these results suggest that DNAM-1 ligands stimulate innate immunity by CD8 alpha(+) DCs as well as NK cells, which efficiently prime cell-mediated tumor-specific immunity. (Blood. 2006;107: 1491-1496) (c) 2006 by The American society of Hematology.