Identification of Th cells in vivo and analysis of differentiation and function of Th2 cells by costimulatory molecules

体内Th细胞的鉴定及共刺激分子对Th2细胞分化和功能的分析

• 批准号: 16616008
• 负责人: AKIBA Hisaya
• 金额: $ 2.5万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16616008/
• 关键词: T cell differentiation; ICOS; B7RP-1; OX40; OX40L; CXCR5; monoclonal antibody; Th1; Th2; Tim; Tim ligand; Tim family; 喘息疾患

1. ICOS is a new member of the CD28 family of costimulatory molecules that is expressed on activated T cells. Its ligand B7RP-1 is constitutively expressed on B cells. Although the blockade of ICOS/B7RP-1 interaction inhibits T cell-dependent Ab production and germinal center formation, the mechanism remains unclear. We speculated that the ICOS/B7RP-1 interaction might be required to up-regulate the expression of a chemokine receptor CXCR5 on CD4 T cells. CXCR5 confers responsiveness to B lymphocyte chemokine (CXCL13). A subset of CD4^+ T cells also express CXCR5, which mediates their migration to the B cell follicles where they provide cognate help to B cells. Thus, CXCR5^+ CD4^+ T cells are referred to as follicular helper T (Th) cells. Previous studies have implicated OX40/OX40 ligand (OX40L) interaction, a pair of the TNFR/TNF family members, in the expression of CXCR5 on CD4^+ T cells. Therefore, we compared the contributions of ICOS/B7RP-1 and OX40/OX40L to the development of CXC … More R5^+ CD4^+ follicular Th cells and GC B cells. Our results indicated that the ICOS/B7RP-1 interaction plays an essential role of follicular Th cells in the spleen and lymph nodes, but the GC formation in lymph nodes is not always dependent on follicular Th cells. On the other hand, a substantial contribution of OX40/OX40L interaction to the development of follicular Th cells and GC B cells was observed only in lymph nodes of certain strains of mice, depending on differential expression of OX40 on follicular Th cells. We also found sub-populations of activated CD4^+ T cells (CXCR5^+ ICOS^+ OX40^- cells, CXCR5^- ICOS^+ OX40^- cells, CXCR5^- ICOS^- OX40^+ cells, and CXCR5^- ICOS^+ OX40^+ cells) in the spleen and LN. It is possible that the three CXCR5^- populations may represent functionally distinct subsets producing Th1 or Th2 cytokines in vivo.2. We demonstrated that IOCS play a role as costimulatory molecules in NKT cell activation, which augments cytokines production and cytotoxic activity. Less

1. ICOS是表达于活化T细胞上的共刺激分子CD 28家族的新成员。其配体B7 RP-1在B细胞上组成型表达。虽然ICOS/B7 RP-1相互作用的阻断抑制了T细胞依赖性Ab的产生和生发中心的形成，但其机制仍不清楚。我们推测ICOS/B7 RP-1相互作用可能是上调CD 4 T细胞上趋化因子受体CXCR 5表达所必需的。CXCR 5赋予对B淋巴细胞趋化因子（CXCL 13）的响应性。CD 4 ^+ T细胞的一个亚群也表达CXCR 5，CXCR 5介导它们迁移到B细胞滤泡，在那里它们为B细胞提供同源帮助。因此，CXCR 5 ^+ CD 4 ^+ T细胞被称为滤泡辅助性T（Th）细胞。先前的研究表明，TNFR/TNF家族的一对成员OX 40/OX 40配体（OX 40 L）相互作用参与了CD 4 ^+ T细胞上CXCR 5的表达。因此，我们比较了ICOS/B7 RP-1和OX 40/OX 40 L在CXC发生中的作用 ...更多信息 R5^+ CD 4 ^+滤泡性Th细胞和GC B细胞。结果表明，ICOS/B7 RP-1相互作用对脾和淋巴结滤泡性Th细胞起重要作用，但淋巴结GC的形成并不总是依赖于滤泡性Th细胞。另一方面，OX 40/OX 40 L相互作用对滤泡性Th细胞和GC B细胞发育的实质性贡献仅在某些品系小鼠的淋巴结中观察到，这取决于滤泡性Th细胞上OX 40的差异表达。我们还在脾脏和LN中发现了活化的CD 4 ^+ T细胞亚群（CXCR 5 ^+ ICOS^+ OX 40 ^-细胞、CXCR 5 ^-ICOS^+ OX 40 ^-细胞、CXCR 5 ^- ICOS^-OX 40 ^+细胞和CXCR 5 ^- ICOS^+ OX 40 ^+细胞）。这三种CXCR 5 β-细胞群可能代表在体内产生Th 1或Th 2细胞因子的功能不同的亚群。我们证明了IOCS在NKT细胞活化中作为共刺激分子发挥作用，这增加了细胞因子的产生和细胞毒活性。少

项目成果

Blockade of B7-H1 on macrophages suppresses CD4+ T cell proliferation by augmenting IFN-γ-induced nitric oxide production

• DOI: 10.4049/jimmunol.175.3.1586
• 发表时间: 2005-08-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Yamazaki, H;Akiba, H;Okumura, K
• 通讯作者: Okumura, K

リンパ球の活性化・機能調節とリンパ球機能分子

淋巴细胞活化/功能调节和淋巴细胞功能分子

• 发表时间: 2005
• 期刊: 日本臨牀 増刊号 臨床免疫学(上) 63
• 作者: Kikuchi Y;Takai T;Kuhara T;Ota M;Kato T;Hatanaka H;Ichikawa S;Tokura T;Akiba H;Mitsuishi K;Ikeda S;Okumura K;Ogawa H;秋葉 久弥
• 通讯作者: 秋葉 久弥

The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo

• DOI: 10.4049/jimmunol.175.4.2340
• 发表时间: 2005-08-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Akiba, H;Takeda, K;Okumura, K
• 通讯作者: Okumura, K

IFN-gamma-mediated negative feedback regulation of NKT-cell function by CD94/NKG2.

CD94/NKG2 干扰素γ介导的 NKT 细胞功能负反馈调节。

• 发表时间: 2005
• 期刊: Blood 106
• 作者: Ota;T.;K.Takeda;H.Akiba;Y.Hayakawa;K.Ogasawara;Y.Ikarashi;S.Miyake;H.Wakasugi;T.Yamamura;M.Kronenberg;D.H.Raulet;K.Kinoshita;H.Yagita;M.J.Smyth;K.Okumura
• 通讯作者: K.Okumura

Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy

• DOI: 10.1084/jem.20031457
• 发表时间: 2004-02-16
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Takeda, K;Yamaguchi, N;Smyth, MJ
• 通讯作者: Smyth, MJ