Basic study of molecular target therapy for autoimmune diseases and immune deficiency diseases based on CD26

基于CD26的自身免疫性疾病及免疫缺陷病分子靶向治疗基础研究

• 批准号: 15209033
• 负责人: MORIMOTO Chikao
• 金额: $ 26.79万
• 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 (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15209033/
• 关键词: CD26; CD45RA; cord T cell; CD86; interference RNA; Caveolin-1; Tetanus Toxid; CD28; 可溶性CD26; リガンド; dipepetidyl peptidase IV; アデノシンデアミナーゼ; リピッドラフト; T細胞シグナル; GVHD

CD26 is a T-cell activation antigen that contains dipeptidyl peptidase IV activity and binds adenosine deaminase. We investigate the role of CD26 in cord blood T-cell activation and signal transduction. We demonstrated that different expression levels of CD26 were observed between cord blood T cells(CBTCs) and peripheral blood T cells(PBTCs) and that CD26(+)CD45RA(+) CBTCs were different compared with CD26(+)CD45RA(+) PBTCs. Moreover, the comitogenic effect of CD26 was not as pronounced in CBTCs as in PBTCs. We also showed that CD26 cross-linking induced less phosphorylation of T-cell receptor-signaling molecules, lymphoid T-cell protein tyrosine kinase(Lck), zeta-associated protein 70(ZAP-70), T-cell receptor zeta(TCRzeta), and linker for activator of T cells(LAT) in CBTCs than in PBTCs. Furthermore, CD26 molecules associated with CD45RA molecules outside lipid rafts in CBTCs. Our results suggest that strong physical linkage of CD26 with CD45RA outside lipid rafts may be responsible f … More or the attenuation of T-cell activation signaling through CD26, which may be responsible for immature immune response and the low incidence of severe graft-versus-host disease in cord blood transplantation.We previously reported that recombinant soluble CD26 enhanced T cell proliferation induced by the recall antigen tetanus toxoid(TT). However, the mechanism involved in this enhancement is not yet elucidated. We now demonstrate that CD26 binds Caveolin-1 on antigen-presenting cells, and that residues 201-211 of CD26 along with the serine catalytic site at residue 630 contribute to binding to caveolin-1 scaffolding domain. In addition, after CD26-caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is phosphorylated, which links to activate NF-kappaB, followed by up-regulation of CD86. Finally, reduced caveolin-1 expression on monocytes inhibits CD26-mediated CD86 up-regulation and abrogates CD26 effect on TT-induced T cell proliferation. Taken together, these results strongly suggest that CD26-caveolin-1 interaction plays a role in the up-regulation of CD86 on monocytes and subsequent engagement with CD28 on T cells, leading to antigen-specific T cell activation. Less

CD26是一种T细胞活化抗原，含有二肽基肽IV活性并结合腺苷脱氨酶。我们研究了CD26在脐带血T细胞激活和信号转移中的作用。我们证明，与CD26（+）CD45RA（+）PBTC相比，CD26（+）CBTC之间观察到CD26的不同表达水平不同，CD26（+）CBTC在CD26（+）CBTC中有所不同，CD26（+）CD45RA（+）CBTC有所不同。此外，在CBTC中，CD26的连质作用不像PBTC中那样明显。我们还表明，CD26交联诱导的T细胞受体信号分子，淋巴样T-细胞蛋白酪氨酸激酶（LCK），ZETA相关蛋白70（ZAP-70）（ZAP-70），T-Cell受体Zeta（TCRZETA）和linker for tlatc for ccttc for ccttc for活化剂（TCRZETA）和petc inctctc inctctctctctctcts（ZAP-70）诱导的T细胞（ZAP-70），ZETA相关蛋白70（ZAP-70）和pectc inctc inctctc inctctctctcts（ZAP-70）。此外，CBTC中脂质筏外的CD26分子与CD45RA分子相关。我们的结果表明，CD26与CD45RA在脂质筏外的紧密身体连接可能是由CD26的T细胞激活信号传导的更多或衰减，这可能导致未成熟的免疫响应，而严重的嫁接性疾病的低流量和脐带血液移植中的严重疗程较低。毒素（TT）。但是，尚未阐明这种增强涉及的机制。现在，我们证明CD26在抗原呈递细胞上结合了Caveolin-1，并保留了CD26的201-211以及住所630的丝氨酸催化位点，有助于与Caveolin-1脚手架结构结合。此外，在加载TT的单核细胞上CD26-Caveolin-1相互作用后，Caveolin-1被磷酸化，与激活NF-kappab相关，然后是CD86的上调。最后，减少的单核细胞上的小窝蛋白-1表达抑制CD26介导的CD86上调，并消除CD26对TT诱导的T细胞增殖的影响。综上所述，这些结果强烈表明CD26-核蛋白-1相互作用在单核细胞上的CD86上调以及随后在T细胞上与CD28的接合起着作用，从而导致抗原特异性T细胞活化。较少的

项目成果

HTLV-I Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L).

HTLV-I Tax 诱导并与 Crk 相关底物淋巴细胞类型 (Cas-L) 相关。

• 发表时间: 2005
• 期刊: Oncogene 24
• 作者: Iwata S;Morimoto C;et al.
• 通讯作者: et al.

Kobayashi S, et al.: "Association of CD26 with CD45RA outside lipid rafts attenuates cord blood T-cell activation."Blood. 103. 1002-1010 (2004)

Kobayashi S 等人：“脂筏外部 CD26 与 CD45RA 的结合会减弱脐带血 T 细胞的活化。”血液。

Kobayashi H, et al.: "Preferential expression of CD9 on human CD4+CD45RA+ naive T cell population responsive to beta2-glycoprotein I."Clin.Exp.Immunol.. (In press).

Kobayashi H 等人：“CD9 在人 CD4 CD45RA 初始 T 细胞群上优先表达对 β2-糖蛋白 I 的反应。”Clin.Exp.Immunol..（正在出版）。

Association of CD26 with CD45RA outside lipid rafts attenuates cord blood T-cell activation.

CD26 与脂筏外 CD45RA 的结合会减弱脐带血 T 细胞的活化。

• DOI: 10.1182/blood-2003-08-2691
• 发表时间: 2004
• 期刊: Blood
• 影响因子: 20.3
• 作者: Kobayashi,Seiji;Ohnuma,Kei;Uchiyama,Masahiko;Iino,Kouichi;Iwata,Satoshi;Dang,NamH;Morimoto,Chikao
• 通讯作者: Morimoto,Chikao

CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-1

• DOI: 10.1073/pnas.0405266101
• 发表时间: 2004-09-28
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Ohnuma, K;Yamochi, T;Morimoto, C
• 通讯作者: Morimoto, C