Blocking 4-1BB/4-1BB ligand interactions prevents herpetic stromal keratitis
Blocking 4-1BB/4-1BB ligand interactions prevents herpetic stromal keratitis
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DOI：
10.4049/jimmunol.171.2.576
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发表时间：
2003-07-15
影响因子：
4.4
通讯作者：
Kwon, BS
中科院分区：
文献类型：
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作者：
Seo, SK;Park, HY;Kwon, BS
单纯疱疹病毒性角膜炎(HSK)是由于反复感染1型单纯疱疹病毒引起的角膜基质慢性炎症过程。我们用小鼠单纯疱疹病毒性角化病(HSK)模型来证明可诱导的T细胞共刺激受体4-1BB及其配体4-1BB配体(4-1BBL)之间的相互作用在该病的发生发展中的重要性。在BALB/c小鼠中，通过阻断4-1BB/4-1BBL的相互作用，或通过缺失4-1BB(-/-)小鼠的4-1BB或通过引入抗4-1BBL的单抗，可预防由疱疹病毒RE株感染的BALB/c小鼠的HSK。大多数渗入感染角膜的T细胞是4-1BB(+)激活的效应细胞，表达细胞表面标志CD44、CD25和/或CD62L，以及趋化因子受体CCR1、CCR2和CCR5，以及有限数量的TCR Vβ链(按丰度顺序为Vbeta8.1/8.2、Vbeta8.3、Vbeta10b和Vbeta5.1/5.2)。细胞表面表型分析表明，4-1BB(-/-)小鼠未能发生HSK与T细胞向角膜基质迁移时CD62L的表达减少有关。
Herpetic stromal keratitis (HSK) is a chronic inflammatory process in corneal stroma that results from recurrent HSV type 1 infection. We used the murine model of HSK to demonstrate the importance of the interaction between an inducible T cell costimulatory receptor, 4-1BB, and its ligand, 4-1BB ligand (4-1BBL), in the development of this disease. In BALB/c mice, HSK ordinarily induced by infection with the RE strain of herpes was prevented by blocking 4-1BB/4-1BBL interaction, either by deleting 4-1BB (in mutant 4-1BB(-/-) mice) or by introducing mAbs against 4-1BBL. The majority of T cells infiltrating the infected corneas were 4-1BB(+) activated effector cells that expressed cell surface markers CD44, CD25, and/or CD62L, as well as chemokine receptors CCR1, CCR2, and CCR5, and a limited number of TCR Vbeta chains (Vbeta8.1/8.2, Vbeta8.3, Vbeta10b, and Vbeta5.1/5.2, in order of abundance). Analysis of cell surface phenotypes showed that the failure to develop HSK in the 4-1BB(-/-) mice was associated with a reduced expression of CD62L at the time of T cell migration into the corneal stroma.