クラスIヒストコンパティビリティアンチゲンの耐性は,エクストラティム的に表現される
G Morahan1, J Allison, J F Miller
1Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Nature
|June 22, 1989
まとめ
自己抗原に対する周辺の耐性は極めて重要です. この研究は,継続的な抗原曝露と低インタールイキン-2 (IL-2) レベルに依存する,自己免疫糖尿病を予防する,トランスゲンマウスにおけるエクストラティム性耐性誘導を示しています.
科学分野:
- 免疫学 免疫学とは
- エンドクリノロジー エンドクリノロジー
- トランスジェニックモデル
背景:
- 自己耐性は,自己免疫性の予防に不可欠です.
- Intrathymic deletionは,知られている耐性メカニズムである.
- 周辺耐性のメカニズム,特に組織特異性抗原に対するメカニズムは,理解が薄いままです.
研究 の 目的:
- 周辺抗原に対する耐性誘導のメカニズムを調査する.
- 臓のβ細胞で自己抗原を発現するトランス遺伝子マウスが,自己免疫反応を回避する方法を探る.
主な方法:
- ラットインスリンプロモーター (RIP-Kb) の下で,クラスIのMHC遺伝子 (H-2Kb) を発現するトランスジェニックマウスの生成.
- 糖尿病前および糖尿病のRIP-Kbマウスからの胸腺および臓細胞における免疫細胞応答 (細胞毒性) の評価.
- リコンビナントインタールイキン-2 (rIL-2) を使用して無反応のインビトロ逆転.
主要な成果:
- 臓のβ細胞でH-2Kbを発現するトランスジェニックマウス (RIP-Kb) は,潜在的アロジェニックの違いにもかかわらず,これらの細胞に対する免疫反応を起こすことができなかった.
- 糖尿病前マウスの臓細胞はH-2Kb標的に対して反応せず,胸腺細胞は反応した.
- 臓細胞の反応不良は,rIL-2によってin vitroで逆転させることができる.
- ベータ細胞が失われ,免疫反応は高齢の糖尿病マウスに回復した.
結論:
- 周辺抗原のプレゼンテーションには,エクストラティム性耐性メカニズムが関与しています.
- この耐性は,抗原の継続的な存在と,IL-2が欠けている局所環境に依存しています.
- これらの発見は,組織特異抗原に対する自己耐性を誘発するための新しい経路を明らかにしています.
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