調節性T細胞1型応答の誘導は,アポリポプロテインEノックアウトマウスの動脈硬化症の発症を減少させます
Ziad Mallat1, Andrea Gojova, Valérie Brun
1Institut National de la Santé et de la Recherche Médicale, INSERM U541, Institut Fédératif de Recherche Circulation Paris VII, Hôpital Lariboisière, Paris, France. mallat@larib.inserm.fr
Circulation
|August 13, 2003
まとめ
調節性T細胞1型 (Tr1) の養子移植は,抑制されたTヘルパー1型 (Th1) 応答を抑制した. この免疫調節により,マウスの実験における動脈硬化症の発生と病変の重症度が著しく低下した.
科学分野:
- 免疫学 免疫学とは
- 心血管研究 循環器科の研究
- T細胞生物学について
背景:
- Tヘルパー1型 (Th1) 免疫反応は,動脈硬化症の促進に関与しています.
- 調節性T細胞1型 (Tr1) は,潜在的な免疫抑制機能を持つ新しいT細胞亜型です.
研究 の 目的:
- Tr1細胞の養子移植がTh1応答を阻害する可能性があるという仮説を検証する.
- Tr1細胞移転が実験的動脈硬化症の発展を制限できるかどうかを判断する.
主な方法:
- オバルブミン (OVA) に特異的なTr1細胞は,試験管内で拡張され,アポリポプロテインEノックアウトマウスに養子縁組で移植されました.
- ネズミは,OVA/完全フレンド補助体 (CFA) 免疫をTr1細胞でまたは Tr1細胞なしで受けました.
- Th1応答は,OVA特異的なIgG2a,インターフェロン-ガンマ,インタールエキン-10のレベルを測定することによって評価されました.
- 動脈硬化性病変のサイズとプラークの組成は9週間後に分析されました.
主要な成果:
- Tr1細胞治療は,OVA特異IgG2aおよびインターフェロン-ガンマの減少,およびインタールユーキン-10の増加によって証明されたTh1応答を大幅に低下させた.
- 調節性免疫応答への明確なシフトは,の細胞で観察されました.
- 動脈硬化性病変の大きさの有意な減少は,胸部大動脈と大動脈シヌスで観察されました.
- Tr1を投与したマウスは,動脈硬化性プラークにマクロファージとT細胞の蓄積が低いことを示した.
結論:
- Tr1型調節性免疫応答は,実験的な動脈硬化症を効果的に軽減する.
- Tr1細胞治療は,免疫応答を調節することによって,動脈硬化症の管理に潜在的可能性を秘めています.
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