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

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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