Molecular biological study on intercellular adhesion molecules involved in activation and differentiation of hematopoietic cells.

参与造血细胞活化和分化的细胞间粘附分子的分子生物学研究。

• 批准号: 02454195
• 负责人: YAGITA Hideo
• 金额: $ 3.97万
• 依托单位: Juntendo University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454195/
• 关键词: adhesion molecules; extracellular matrix receptor; T cell activation; tolerance; integrins; CD4; CD8; CD2; CD48; LFA-1; ICAM-1; LFAー1; ICAMー1; T細胞分化; CD_2; CD11a; 18; CD54

(1)We revealed that CD4 and CD8 regulate IL-2 response of T cells via activation of p56^<lck> associated with them.(2)We demonstrated that CD2-mediated signal plays an important role in T and NK cell activation.(3)We revealed that CD48 is the predominant ligand for mouse CD2.(4)We also demonstrated that CD48 is the second ligand for human CD2 other than LFA-3.(5)We found that administration of anti-CD2 and anti-CD48 monoclonal antibodies led to a specific acceptance of mouse cardiac allografts.(6)We found that administration of anti-LFA-1 and anti-ICAM-1 monoclonal antibodies led to a specific acceptance of mouse and rat cardiac allografts, which resulted from the induction of allospecific peripheral tolerance by clonal anergy. We also found that anti-VLA-4 and anti-VCAM-1 monoclonal antibodies had a similar effect although it was less efficient.(7)We found that administration of anti-LFA-1 and anti-ICAM-1 monoclonal antibodies suppressed the pathogenesis of adjuvant arthritis in rats, collagen-induced arthritis in mice, and diabetes in NOD mice.(8)We found that anti-VLA-4 and anti-VCAM-1 monoclonal antibodies specifically inhibited erythropoiesis in vitro and in vivo.(9)We established monoclonal antibodies to mouse and rat vitronectin receptor, VLA-4, and VLA-5, and demonstrated that the interaction with fibronectin mediated by these integrins are critically involved in regulating T and mast cell activation.(10)We established monoclonal antibodies to mouse VLA-1, VLA-2, VLA-3, and VLA-6, and examined the expression and function of these collagen and/or laminin receptors on hematopoietic cells.(11)We revealed that beta_1 integrin-mediated interaction with extracellular matrix proteins regulates inflammatory cytokine gene expression in synovial fluid mononuclear cells of rheumatoid arthritis patients.

(1)我们发现CD4和CD8通过激活与它们相关的p56^<lck>来调节T细胞的IL-2应答。(2)我们证明了cd2介导的信号在T和NK细胞活化中起重要作用。(3)我们发现CD48是小鼠CD2的主要配体。(4)我们还证明了CD48是人类CD2的第二个配体，仅次于LFA-3。(5)我们发现给药抗cd2和抗cd48单克隆抗体导致小鼠心脏异体移植特异性接受。(6)我们发现，抗lfa -1和抗icam -1单克隆抗体可诱导小鼠和大鼠心脏异体移植产生特异性接受，这是由于克隆能量诱导异体外周耐受。我们还发现抗vca -4和抗vcam -1单克隆抗体具有相似的效果，尽管效率较低。(7)我们发现抗lfa -1和抗icam -1单克隆抗体可抑制大鼠佐剂性关节炎、小鼠胶原诱导关节炎和NOD小鼠糖尿病的发病机制。(8)我们发现抗vca -4和抗vcam -1单克隆抗体在体外和体内特异性抑制红细胞生成。(9)我们建立了小鼠和大鼠玻璃体连接蛋白受体vla4和vla5的单克隆抗体，并证明了这些整合素介导的与纤维连接蛋白的相互作用在调节T细胞和肥大细胞活化中起关键作用。（10）我们建立了针对小鼠vla1、vla2、vla3和vla6的单克隆抗体，并检测了这些胶原和/或层粘连蛋白受体在造血细胞上的表达和功能。（11）我们发现β _1整合素介导的与细胞外基质蛋白的相互作用调节类风湿关节炎患者滑液单个核细胞中炎症细胞因子基因的表达。

项目成果

T.Nakamura: "Acitivation of a NK clone upon target cell binding via CD2." Eur.J.Immunol.21. 831-834 (1991)

T.Nakamura：“通过 CD2 结合靶细胞后激活 NK 克隆。”

Isobe,M.: "Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1." Science. 255. 1125-1127 (1992)

Isobe,M.：“用 ICAM-1 和 LFA-1 抗体治疗后对心脏同种异体移植物的特异性接受。”

Kato K.: "CD48 is a counter-receptor for mouse CD2 and involved in T cell activation." J.Exp.Med.176. 1241-1249 (1992)

Kato K.：“CD48 是小鼠 CD2 的反受体，参与 T 细胞激活。”

Kakimoto,K.: "The effect of anti-adhesion molecule antibody on the development of collagen-induced arthritis." Cell.Immunol.142. 326-337 (1992)

Kakimoto,K.：“抗粘附分子抗体对胶原诱导的关节炎发展的影响。”

T.Nakamura: "Relative contribution of CD2 and LFAー1 to murine T and NK cell functions." J.immunol.145. 3628-3634 (1990)

T.Nakamura：“CD2 和 LFA-1 对小鼠 T 和 NK 细胞功能的相对贡献。J.immunol.145 (1990)。