Molleculor Biological Analysis of the role of B71BB1 in contact dermatitis

B71BB1 在接触性皮炎中作用的分子生物学分析

• 批准号: 06670855
• 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 General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670855/
• 关键词: Contact Dermatitis; T cell Activation; Costimulatory molecnles; CD80 (B7-1); CD86 (B7-2); Langerhans cell; T cell; T細胞; CD80抗原; CD86抗原

Recently, an alternative CD28 ligand, CD86 (B70/B7-2) has been identified on activated B cells. It has been also found that CD86 may play an important role for costimulation of T cells in a primary immune response (Nature : 366,76-79,1993). These finding led us to determine whether CD80 and CD86 antigens express on Langerhans cells (LC) and costimulatory molecules transduced signals play a role in T cell activation in contact hypersensitivity.We first examined CD80, CD86 expression on EC of organ cultured human skin, by staining with the monoclonal anti CD80 (L307), anti CD86Ab (IT2). Keratinocyte (KC) expressed little CD80, CD86, but both CD80 and CD86 molecules on Langerhans cell (LC) have been expressed extensively strongly after culturing. Both CD86 and CD 86 molecules have been detected in contact ddermatitis, atopic dermatitis and psoriasis. In these cases, expression of CD86 was predominantly induced. To determine whether IT2 react with 70KD glycoprotein on LC,immunoblotting method was conducted. IT2 was reacted mainly with the 70KD peptide of LC.We also examined the effect of mAb anti-CD80 or mAb anti-CD86 on the capacity of cultured EC to stimulate proliferation of allogeneic peripheral blood mononuclear cellc (PBMC). Both anti CD80 mAb and anti CD86 mAb efficiently inhibited the mixed epidermal cell-lymphocyte reaction.These data indicate that CD86 (B70/B7-2) antigen expressed on LC may play an important role for costimulation of T cells in a primary immune response ; contact dermatitis.

最近，在活化的 B 细胞上发现了另一种 CD28 配体 CD86 (B70/B7-2)。还发现CD86可能在初级免疫应答中对T细胞的共刺激发挥重要作用(Nature：366，76-79，1993)。这些发现使我们确定 CD80 和 CD86 抗原是否在朗格汉斯细胞 (LC) 上表达，以及共刺激分子转导的信号是否在接触性超敏反应中的 T 细胞激活中发挥作用。我们首先检查了器官培养的人皮肤 EC 上的 CD80、CD86 表达，通过用单克隆抗 CD80 (L307)、抗 CD86Ab (IT2) 染色。角质形成细胞(KC)很少表达CD80、CD86，但朗格汉斯细胞(LC)上的CD80和CD86分子在培养后已广泛强烈表达。 CD86 和 CD 86 分子均在接触性皮炎、特应性皮炎和牛皮癣中检测到。在这些情况下，CD86 的表达主要被诱导。为了确定IT2是否与LC上的70KD糖蛋白反应，进行了免疫印迹法。 IT2主要与LC的70KD肽反应。我们还检测了mAb抗CD80或mAb抗CD86对培养的EC刺激同种异体外周血单核细胞（PBMC）增殖能力的影响。抗CD80 mAb和抗CD86 mAb均能有效抑制混合表皮细胞-淋巴细胞反应。这些数据表明，LC上表达的CD86 (B70/B7-2)抗原可能在初次免疫反应中对T细胞的共刺激发挥重要作用；接触性皮炎。

项目成果

横関博雄: "アトピー性皮膚炎Q&A(西岡 清 編)" 医薬ジャーナル社, 141 (1995)

横关博夫：“特应性皮炎问答（西冈清编辑）” Iyaku Journalsha，141（1995）

Hiroo Yokozeki: "Functional CD86(B7-2) on cultured human Langerhas cells" J.Invest.Dermctol.(in press). (1996)

Hiroo Yokozeki：“培养的人 Langerhas 细胞上的功能性 CD86(B7-2)”J.Invest.Dermctol.（出版中）。

Hiroo Yokozeki: "Experimental study for the development of an in vitro Test for contact allergens." Int.Arch Allergy Immnol. 106. 394-400 (1995)

Hiroo Yokozeki：“开发接触性过敏原体外测试的实验研究。”

Ichiro Katayama: "Induction and characterization of mast cell colonies by culture supernatant of retinoid acid-treated mouse keratinocytes" Int.Arch.Allerg.Immunol. 100. 328-332 (1993)

Ichiro Katayama：“通过视黄酸处理的小鼠角质形成细胞的培养上清液诱导和表征肥大细胞集落”Int.Arch.Allerg.Immunol。

Hiroo Yokozeki: "Experimentol study for Developing an In Vitro Test for contact allengen I,Primany Activation of Hepten-specfic T cell by Hapten-congvated EC" Int.Arch.Allerg.Immunol. (in press).

Hiroo Yokozeki：“开发接触性过敏原 I 体外测试的实验研究，通过半抗原结合 EC 对 Hepten 特异性 T 细胞的初步激活”Int.Arch.Allerg.Immunol。