Role of Langerhans Epidermal Cells in Protection against Herpes Simplex Virus Infections

为了研究表皮朗格汉斯细胞（LC）在抵抗单纯疱疹病毒（HSV）感染中的作用，本实验采用同种表皮细胞（EC）和紫外线灭活的HSV抗原对经HSV免疫的BALB/c小鼠非贴壁脾细胞进行培养。培养5天后，用^ 3h -胸腺嘧啶掺入法测定T细胞依赖性增殖反应。培养前用抗ia ^d单克隆抗体加补体处理EC可阻止其增殖，这表明LC诱导了免疫T细胞的刺激。将这些受刺激的脾细胞转移到经皮感染的裸鼠身上，皮肤中的病毒滴度明显降低，带状虫状皮肤病变的形成完全被抑制。另一方面，单纯用HSV抗原培养或用抗ia ^d单克隆抗体加补体处理的HSV抗原和EC培养的未刺激细胞的转移，导致病毒的清除和病变的发展缓慢。这些结果表明，EC作为辅助细胞在控制皮肤HSV感染中起重要作用。此外，在制备EC前1至3天将皮肤暴露在紫外线下会导致细胞增殖的剂量依赖性损伤。这种紫外线诱导的EC副细胞功能损伤伴随着Ia^+ EC数量的平行减少。从受辐射小鼠获得的EC刺激的免疫T细胞不能有效清除HSV，并允许裸小鼠发生带状虫状皮肤病变。相反，正常ec刺激的免疫T细胞完全阻止了带状虫状皮疹的形成。此外，在皮内接种HSV前2天，在剃光的小鼠腹部皮肤上进行紫外线照射，与对照小鼠相比，感染的严重程度增加，潜伏期发生率更高。这些研究表明，体内皮肤紫外线照射在体外和体内均可破坏LC的免疫功能，并影响HSV的发病机制。少

To investigate the role of epidermal Langerhans cells (LC) in resistance to herpes simplex virus (HSV) infection, nonadherent spleen cells taken from BALB/c mice immunized with HSV were cultured with syngeneic epidermal cells (EC) and ultraviolet light-inactivated HSV antigen. After five days of culture, T cell-dependent proliferative response was determined by ^3H-thymidine incorporation. Treatment of EC with anti-Ia^d monoclonal antibody plus complement before cultivation prevented this proliferation, which suggested that LC induced stimulation of immune T cells. When these stimulated spleen cells were transferred to intracutaneously infected nude mice, the virus titer in the skin was reduced markedly and the formation of zosteriform skin lesions was completely inhibited. On the other hand, transfer of unstimulated cells, which were cultured with HSV antigen only or wiht HSV antigen and EC treated with anti-Ia^d monoclonal antibody plus complement, resulted in delaved viral clearance … More and development of the lesions. These results indicate that EC are of importance as accessory cells in the control of cutaneous HSV infection. Furthermore, exposure of the skin to UV light 1 to 3 days before preparation of EC resulted in dose-dependent impairment of the proliferation. This UV-induced impairment of the accessory cell function of EC was accompanied by a parallel reduction of the number of Ia^+ EC. Immune T cells stimulated with EC obtained from irradiated mice did not effectively clear HSV and allowed development of zosteriform skin lesions in nude mice. In contrast normal-EC-stimulated immune T cells completely prevented the formation of a zosteriform rash. In addition, mice irradiated with UV on shaved midflank skin 2 days before intracutaneous inoculation of HSV showed increased severity of infection and a highter incidence of latency compared with control mice. These studies indicate that in vivo UV irradiation of the skin abrogates the immune function of LC both in vitro and in vivo, and affects HSV pathogenesis. Less