Bystander activation involving T lymphocytes in herpetic stromal keratitis
Bystander activation involving T lymphocytes in herpetic stromal keratitis
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DOI：
10.4049/jimmunol.167.5.2902
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发表时间：
2001-09-01
影响因子：
4.4
通讯作者：
Rouse, BT
中科院分区：
文献类型：
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作者：
Deshpande, S;Zheng, M;Rouse, BT
小鼠角膜的单纯疱疹病毒感染可导致免疫病理病变的发展，称为疱疹性间质角膜炎（HSK）。这种病变也发生在tcr转基因小鼠回交到SCID （TgSCID）中，这些小鼠无法产生可检测的hsv特异性免疫反应。目前的研究表明，这种小鼠的病变表达依赖于持续的病毒复制，而在免疫能力强的小鼠中，即使在感染后4天终止病毒复制，病变也会发生。TgSCID小鼠体内的持续复制被认为是对侵入角膜的CD4(+) T细胞产生激活刺激的必要条件。TgSCID的病变对环孢素A的控制有抗性，但对雷帕霉素的治疗有抑制作用。这一结果被解释为表明T细胞激活涉及非tcr介导的细胞因子驱动的旁观者机制。旁观者激活也被证明在免疫正常小鼠的HSK病变中起作用。因此，在免疫正常的DO11.10小鼠中，病变主要由与HSV无反应的KJ1.26(+) ova特异性CD4(+) T细胞主导。此外，停留在BALB/c小鼠眼感染中的KJ1.26(+) HSV非免疫细胞在FISK病变中被证实。这些结果为选择新的策略来管理HSK（人类失明的重要原因）提供了见解。
Herpes simplex virus infection of mouse corneas can lead to the development of an immunopathological lesion, termed herpetic stromal keratitis (HSK). Such lesions also occur in TCR-transgenic mice backcrossed to SCID (TgSCID) that are unable to mount detectable HSV-specific immune responses. The present study demonstrates that lesion expression in such mice depends on continuous viral replication, whereas in immunocompetent mice, lesions occurred even if virus replication was terminated at 4 days after infection. The continuous replication in TgSCID mice was considered necessary to produce an activating stimulus to CD4(+) T cells that invade the cornea. Lesions in TgSCID were resistant to control by cyclosporin A, but were inhibited by treatment with rapamycin. This result was interpreted to indicate that T cell activation involved a non-TCR-mediated cytokine-driven bystander mechanism. Bystander activation was also shown to play a role in HSK lesions in immunocompetent mice. Accordingly, in immunocompetent DO11.10 mice, lesions were dominated by KJ1.26(+) OVA-specific CD4(+) T cells that were unreactive with HSV. In addition, KJ1.26(+) HSV nonimmune cells parked in ocularly infected BALB/c mice were demonstrable in FISK lesions. These results provide insight for the choice of new strategies to manage HSK, an important cause of human blindness.