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)B7分子在AD和CD中的表达在本研究中，我们研究了共刺激分子在AD和CD中的表达和功能，这些分子在正常对照组中未检测到。在异位性皮炎的非病变皮肤中，检测到CD 86而非CD 80。皮损型特应性皮炎CD 80表达率为42%，而CD 86全部表达。CD皮损中CD 86的表达强于CD 80，我们进行了抑制试验。抗CD 86单抗完全抑制了DP粗提物刺激的表皮T细胞作为抗原提呈细胞的增殖，提示CD 86在AD和CD的发病机制中可能起重要作用。诱导郎格罕细胞上弱B7-1（CD 80）和中等B7-2（CD 86）表达以及器官培养的小鼠皮肤中两种分子的mRNA表达。皮内注射半抗原化的EC可引起半抗原特异性的接触敏感性，当半抗原化的EC与抗B7 -2（CD 86）或B7-1（CD 80）抗体孵育后注射到小鼠体内，所产生的接触敏感性反应降至对照反应的50%以下。抗B7 -2和抗B7 - 1单抗在体外也能抑制半抗原特异性淋巴细胞增殖和同种异体混合淋巴细胞反应，提示半抗原诱导的共刺激信号在小鼠接触性过敏中起重要作用。

项目成果

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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）

Yokozaki H,Katayama I,Ohki O,Matsunaga T,Watanabe K,Satho Tm asuma M,Okumura K,Nishioka K: "Functional CD86 (B7-2/B70) on cultured human Langerhans cells" J Invest Dermatol. 106. 147-153 (1995)

Yokozaki H、Katayama I、Ohki O、Matsunaga T、Watanabe K、Satho Tm asuma M、Okumura K、Nishioka K：“培养的人朗格汉斯细胞上的功能性 CD86 (B7-2/B70)”J Invest Dermatol。