Hendricks R L, Janowicz M, Tumpey T M
Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago 60612.
J Immunol. 1992 Apr 15;148(8):2522-9.
Previous studies have revealed that the RE strain of HSV type 1 (HSV-1) induces a tissue-destructive inflammatory response in the mouse cornea that is mediated by CD4 T lymphocytes, whereas the KOS strain of HSV-1 preferentially activates CD8 T lymphocytes in the cornea. Langerhans cells (LC) normally reside only at the periphery of the cornea but can migrate centripetally after HSV-1 infection. We studied the relative contribution of LC to the corneal inflammation induced by the KOS and RE strains of HSV-1. Ten days after infection, the central one-third of RE HSV-1-infected corneas contained an average of 5.7 LC/high-power field compared with 0.6 LC/high-power field in KOS-infected corneas. We hypothesized that the increased density of LC in RE HSV-1-infected corneas at the time of T lymphocyte infiltration contributed to the preferential activation of CD4 T lymphocytes in these corneas. To test this hypothesis, we gave mice a low dose of UV-B corneal irradiation (150 mJ/cm2) 1 day before infection with HSV-1. UV-B irradiation effectively prevented the migration of LC into the central cornea when measured 10 or 21 days after corneal infection with either HSV-1 strain. UV-B corneal irradiation had no effect on the CTL response to HSV-1 Ag in the regional lymph nodes after corneal infection with KOS or RE HSV-1. The delayed-type hypersensitivity response induced by both strains of virus, when measured 8 and 14 days after corneal infection, was significantly reduced by UV-B irradiation. UV-B irradiation significantly reduced the incidence (p = 0.0023) and severity (p = 0.0008) of corneal stromal disease induced by RE HSV-1 but did not significantly affect the stromal disease induced by KOS HSV-1. To distinguish between the effect of UV-B treatment on the afferent and efferent arms of the Ir in mice, we administered UV-B treatment to one eye, followed 24 h later by RE HSV-1 infection of both eyes. These mice developed a normal delayed-type hypersensitivity response, and stromal inflammation developed normally in the untreated eye. However, stromal inflammation was significantly reduced in the treated eye. Our findings suggest that LC play a critical role in the activation of HSV-reactive CD4 T lymphocytes in the cornea. Moreover, the type of corneal inflammation induced by different strains of HSV-1 may reflect their differential capacity to induce LC migration into the central cornea.
先前的研究表明，1型单纯疱疹病毒（HSV-1）的RE株在小鼠角膜中诱导一种由CD4 T淋巴细胞介导的组织破坏性炎症反应，而HSV-1的KOS株在角膜中优先激活CD8 T淋巴细胞。朗格汉斯细胞（LC）通常仅存在于角膜周边，但在HSV-1感染后可向心性迁移。我们研究了LC对HSV-1的KOS株和RE株诱导的角膜炎症的相对贡献。感染后10天，RE HSV-1感染的角膜中央三分之一平均每高倍视野含5.7个LC，而KOS感染的角膜每高倍视野含0.6个LC。我们推测，在T淋巴细胞浸润时，RE HSV-1感染的角膜中LC密度增加有助于这些角膜中CD4 T淋巴细胞的优先激活。为验证这一假设，我们在小鼠感染HSV-1前1天给予低剂量的UV-B角膜照射（150 mJ/cm2）。在用任何一种HSV-1株感染角膜后10天或21天测量时，UV-B照射有效地阻止了LC向角膜中央迁移。UV-B角膜照射对KOS或RE HSV-1感染角膜后区域淋巴结中对HSV-1抗原的CTL反应没有影响。在用两种病毒株感染角膜后8天和14天测量时，UV-B照射显著降低了由两种病毒株诱导的迟发型超敏反应。UV-B照射显著降低了RE HSV-1诱导的角膜基质疾病的发生率（p = 0.0023）和严重程度（p = 0.00），但对KOS HSV-1诱导的基质疾病没有显著影响。为区分UV-B处理对小鼠免疫反应的传入和传出臂的影响，我们对一只眼睛进行UV-B处理，24小时后对两只眼睛进行RE HSV-1感染。这些小鼠产生了正常的迟发型超敏反应，未处理的眼睛中基质炎症正常发展。然而，处理过的眼睛中基质炎症显著减轻。我们的研究结果表明，LC在角膜中HSV反应性CD4 T淋巴细胞的激活中起关键作用。此外，不同株HSV-1诱导的角膜炎症类型可能反映了它们诱导LC向角膜中央迁移的不同能力。
