Resolution of HSV corneal infection in the absence of delayed-type hypersensitivity

The role of delayed-type hypersensitivity (DTH) in the resolution of herpes simplex virus type 1 (HSV-1) ocular infection was examined. Infection of Balb/c mice on the sacrificed cornea with HSV-1 resulted in sensitization for DTH. This response, demonstrable by swelling of the ear following inoculation with ultraviolet-irradiated virus, was optimal 7 days postinfection. The reaction was immunologically specific and characterized histologically by a predominately mononuclear cell infiltrate. DTH responsiveness could be completely abrogated if the mice were inoculated intravenously with an attenuated strain of HSV-17 days before corneal infection. DTH-unresponsive mice were, nevertheless, resistant to corneal challenge with sublethal or lethal doses of HSV-1. Resistance was accompanied by a greater than 30-fold reduction in infectious virus in the eye 24 hr post challenge. A cellular infiltrate characteristic of a DTH response was not observed within the cornea during virus clearance. Tolerance was restricted to DTH, as antibodies to HSV antigens could be readily demonstrated 6-7 days after intravenous virus immunization. These antibodies may have contributed to the resistance observed. The results establish that neither a systemic nor local DTH response is required by the host to resist HSV-1 ocular infection.