B7-1/B7-2共刺激は,低密度リポプロテイン受容体欠乏マウスにおけるプラーク抗原特異性T細胞反応とアテロゲネシスを調節する

Chiara Buono¹, Hong Pang, Yasushi Uchida

¹Immunology Research Division and the Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass 02115, USA.

Circulation

|April 21, 2004

まとめ

B7-1/B7-2共刺激経路は,動脈硬化を引き起こすT細胞応答に不可欠です. この経路を遮断すると,小鼠における病変の発生と炎症性T細胞の活性が低下する.

科学分野:

免疫学免疫学とは
心血管研究循環器科の研究
動脈硬化症の病原性病原性

背景:

T細胞の反応,特に酸化LDLやHSP60のような損傷抗原に対するインターフェロン・ガンマ (IFN-ガンマ) 産生は,動脈硬化疾患の進行とプラークの不安定性に関与しています.
B7-1とB7-2は,T細胞活性化に不可欠な抗原を呈現する細胞の重要な共刺激分子である.

研究の目的:

動脈硬化にT細胞媒介による影響におけるB7-1/B7-2共刺激の役割を調査する.
動脈硬化にT細胞の影響がB7-1/B7-2共刺激に依存するという仮説を検証する.

主な方法:

利用したB7-1/B7-2/LDL受容体 (LDLR) 欠乏症のマウスとLDLR欠乏症の対照マウスは,それぞれ8週間と20週間,高コレステロールの食事を与えられた.
分析された血清コレステロール,動脈硬化性病変の範囲と現象型,および,HSP60で刺激されたCD4+T細胞によるIFN-ガンマ/インターリューキン-4の産生 in vitro.

主要な成果:

B7-1とB7-2の欠如は,コレステロールダイエット中のLDLR欠乏マウスの早期動脈硬化症の発症を著しく減少させた.
コレステロールを摂取したB7欠乏マウスのCD4+T細胞は,対照群と比較してHSP60への反応として,IFN-ガンマを著しく少なく生成した.

結論:

B7-1とB7-2分子は,動脈硬化病変の発達を調節する.
これらの共刺激性分子は,損傷抗原に特異的なT細胞のプライミングに不可欠です.
B7-CD28経路は,動脈硬化症における免疫調節のための潜在的な治療標的を表しています.

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