Dynamism of immune cells in immune-tissue formation

免疫细胞在免疫组织形成中的动态

• 批准号: 15078203
• 负责人: MATSUSHIMA Kouji
• 金额: $ 64.06万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15078203/
• 关键词: chemokine; dendritic cells; virus; lymph node; migration; CTL; memory; ウイルス; TNF-α; 炎症; 免疫組織; 胸腺; 免疫細胞移動

This project was intended to reveal the regulation of dynamic trafficking of subset of immune cells by chemokines to form immune-tissues in response to pathogen infection. As a result, the following points were found. 1. myeloid dendritic cells (mDCs) capture and process antigens, transport them from the tissue to the draining lymph nodes (LNs) and act as an antigen presenting cells, whereas plasmacytoid DCs (pDCs) directly migrate into inflamed LNs through HEV to help APC function of mDCs 2. nTreg home to the paracortex area of peripheral LNs through HEV in a CCR7 dependent manner and make cluster with subset of DCs 3. a primary response during re-challenge significantly contributes to memory T cell. Upon re-challenge, the skewed Vb usage and T-cell receptor (TCR) repertoire of pre-existing memory T cells is partly corrected by diversity in a newly primed (primary) T cell population. Importantly, this primary population expands more vigorously in a subsequent antigen encounter. These findings indicate that memory T cell populations evolve over multiple challenges, favoring memory T cells generated in more recent encounters, and suggest that these primary populations have essential roles in the perpetuation of antigen-specific T cell populations.

本项目旨在揭示趋化因子对免疫细胞亚群动态运输的调节，以形成免疫组织响应病原体感染。结果发现：1.髓样树突状细胞（mDC）捕获并加工抗原，将它们从组织转运到引流淋巴结（LN）并充当抗原呈递细胞，而浆细胞样DC（pDC）通过HEV直接迁移到发炎的LN中以帮助mDC的APC功能2。nTreg以CCR7依赖性方式通过HEV归巢到外周LN的副皮质区，并与DC 3的子集形成簇。在再激发期间的初级应答显著有助于记忆T细胞。在再激发时，预先存在的记忆T细胞的偏斜的Vb使用和T细胞受体（TCR）库通过新引发的（原代）T细胞群体中的多样性而部分校正。重要的是，这种初级群体在随后的抗原遭遇中更有力地扩增。这些发现表明，记忆T细胞群体在多重挑战中进化，有利于在最近的遭遇中产生的记忆T细胞，并表明这些初级群体在抗原特异性T细胞群体的永久化中具有重要作用。

项目成果

Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellula carcinoma : clinical safety.

经导管肝动脉栓塞与瘤内树突状细胞输注联合治疗肝细胞癌：临床安全性。

• 发表时间: 2007
• 期刊: Clin Exp Immunol. 147(2)
• 作者: Nakamoto Y;et al.
• 通讯作者: et al.

Tomita S, et al.: "T cell-specific disruption of aryl hydrocarbon receptor nuclear translocator gene causes resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced thymic involution."J.Immunol.. 171. 4113-4120 (2003)

Tomita S 等人：“T 细胞特异性破坏芳基碳氢化合物受体核易位基因，导致对 2,3,7,8-四氯二苯并-对-二恶英诱导的胸腺退化产生抗性。”J.Immunol.. 171. 4113

Mobilization of Dendritic Cell Precursors Into the Circulation by Administration of MIP-1 a in Mice.

通过在小鼠中施用 MIP-1a 将树突状细胞前体动员到循环中。

• 发表时间: 2004
• 期刊: J Natl Cancer Inst. 96(3)
• 作者: Zhang Y;et al.
• 通讯作者: et al.

Enhanced natural killer cell binding and activation by low-fucose IgG1 antibody results in potent antibody-dependent cellular cytotoxicity induction at lower antigen density

• DOI: 10.1158/1078-0432.ccr-04-2263
• 发表时间: 2005-03-15
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Niwa, R;Sakurada, M;Shitara, K
• 通讯作者: Shitara, K

Exacerbation of granuloma formation in interleukin-1 receptor antagonist-deficient mice with impaired cell migration associated with Th2 cytokine production.

在白细胞介素 1 受体拮抗剂缺陷小鼠中，与 Th2 细胞因子产生相关的细胞迁移受损，肉芽肿形成加剧。

• 发表时间: 2005
• 期刊: J Immunol. 174
• 作者: Iizasa H;et al.
• 通讯作者: et al.