Induction of tolerance of contact hypersensitivity by blocking CD28 Signal

通过阻断 CD28 信号诱导接触性超敏反应耐受

• 批准号: 08670952
• 负责人: YOKOZEKI Hiroo
• 金额: $ 1.28万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670952/
• 关键词: Langerhans cells; Contact allergy; B7 antigen; Cytokines; atopic dermatitis; CD80; CD86; cytokine

1) The B7 nolecules expression in AD and CDIn the present study, we investigated the expression and function of co-stimulatory molecules in AD and CD.These molecules were not detected in normal control subjects. In non-lesional skin of atopic dermatits, CD86 but not CD80 was detected. Inlesional atopic dermatits, CD80 was expressed 42%, while CD86 was expressed in all case. Similar results of the stronger expression of CD86 over CD80 was detected in the lesional skin in CD.We conducted the inhibition test. Anti-CD86 mab completely inhibite T cell proliferation stimulated with crude extract of DP in the epidermal cell as antigen presenting cells.These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of AD and CD.2) In vitroThe hapten, TNBS,induced weak B7-1 (CD80) and moderate B7-2 (CD86) expression on Langerhans cells and mRNA expression of both molecules in organ-cultured murine skin. The intradermal injection of haptenated EC induced hapten-specific contact sensitivity.When hapten-treated EC were injected into mice after incubation with anti-B7-2 (CD86) or B7-1 (CD80) antibody the resultant contact sensitivity reaction was decreased to less than 50% of the control reaction. Anti-B7-2 and antiB7-1mAb also inhibited hapten-specific lymphocyte proliferation or the allogeneic mixed lymphocyte reaction in vitro.These data indicated that costimulatory signals induced by a hapten on Langerhans cells play an important roles in the induction of contact sensitivity in mice.

1）在AD和CDIN中，B7 noLecules表达在本研究中，我们研究了AD和CD中共刺激分子的表达和功能。在正常对照组中未检测到这些分子。在非特应性皮肤的非静态皮肤中，检测到CD86但未检测到CD80。不静电特应性皮肤，CD80表示42％，而CD86在所有情况下均表达。在CD中，在病变的皮肤中检测到CD86在CD80上的表达更强的结果。我们进行了抑制测试。抗CD86 mAb完全抑制了表皮细胞中DP的粗提取物刺激的抗原提取物作为抗原呈现细胞。这些数据表明，这些数据表明，在Langerhans细胞上表达的CD86在vist.2中可能起重要作用。 Hapten，TNBS，诱导兰格汉细胞上的弱B7-1（CD80）和中等B7-2（CD86）表达，以及在器官培养的鼠皮中两个分子的mRNA表达。触发性EC诱导的触觉特异性接触敏感性的皮内注射。当与抗B7-2（CD86）或B7-1（CD80）抗体孵育后，将抗触觉治疗的EC注入小鼠时，将所得的接触反应降低至降低控制反应的50％。抗B7-2和Antib7-1mAb还抑制了体外的抗触发特异性淋巴细胞增殖或同种异体混合淋巴细胞反应。这些数据表明，这些数据表明，由langerhans细胞上的hapten诱导的costimulation信号在洛格汉细胞上具有重要作用在诱导小鼠接触效率中起着重要作用。 。

项目成果

Satoh T et al: "Cycloshos rhamide-indudd. blood and tissue . eosinoplil in contact glusitirity-mechansm of haptenatd-induct eosinopblieu" Eu J.Iwnunol. 27. 85-91 (1997)

Satoh T 等人：“Cycloshos rhamide-indudd。血液和组织。接触 glusitirity-半抗原诱导 eosinopblieu 机制中的 eosinoplil”Eu J.Iwnunol。

Igawa K et al: "Topical gluco corticoid augments both allegic and nunallirgic cutcneous readia in mice when arplied at the aftait stagy of CI" Allergology Intern. 46. 33-41 (1997)

Ikawa K 等人：“当在 CI 阶段使用时，局部糖皮质激素可增强小鼠的过敏性和非过敏性皮肤反应”，过敏学实习生。

横関博雄: "自己免疫性皮膚疾患:免疫疾患-分子メカニズムから疾患診断診療まで" 羊工社, 136-137 (1996)

Hiroo Yokozeki：“自身免疫性皮肤病：免疫疾病 - 从分子机制到疾病诊断和治疗” Yokosha，136-137（1996）

横関 博雄: "自己免疫性皮膚疾患:免疫疾患-分子メカニズムから病〓診断治療まで" 羊工者, 136-137 (1996)

Hiroo Yokozeki：“自身免疫性皮肤病：免疫性疾病 - 从分子机制到疾病诊断和治疗” Hitsuji Kosha，136-137（1996）

横関博雄: "アトピー性皮膚炎:病態と治療" 医薬ジャーナル, 36-52 (1997)

Hiroo Yokozeki：“特应性皮炎：病理学和治疗”医药杂志，36-52（1997）