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Mechanism of Acquired Resistance to Herpes Simplex Virus Infection as Studied in Nude Mice

Department of Microbiology, School of Medicine, Kyushu University, Fukuoka, 812 Japan

The role of antibody and cell-mediated immunity in the resistance of adult mice to intracutaneous infection with herpes simplex virus type 1 (HSV-1) was studied in nu/nu and nu/+ mice. In nu/+ mice, local skin lesions began to appear at the site of inoculation on the 4th day after intracutaneous challenge with the virulent Hayashida strain of HSV-1. Zosteriform skin lesions were observed in some animals. Almost complete regression of the lesions had occurred by the 16th day p.i. In contrast, all of the nu/nu mice that developed local skin lesions died after development of severe zosteriform skin lesions. After repeated intraperitoneal inoculations with the avirulent SKa strain of HSV-1, nu/nu mice did not produce detectable amounts of neutralizing antibody and succumbed to infection, indicating no development of resistance.

Passively transferred neutralizing antibody prevented nu/nu mice from developing zosteriform skin lesions by the Hayashida strain of HSV-1, as long as the minimum concentration of serum antibody was maintained and prolonged their survival time. Adoptive transfer of 1.0 x 10⁷ immune nu/+ spleen cells to nu/nu mice provided almost complete recovery from infection with production of sporadic low levels of anti-HSV antibody. The protective action of the immune spleen cells was lost after pre-treatment with anti- serum and fresh guinea pig serum prior to transfer of the cells. These data indicate that T cell-mediated cellular immunity plays a major role in recovery from intracutaneous HSV infection in mice, while antibody-mediated protection due to passive administration of HSV antibody is effective only in limiting the spread of virus.

^* Present address: Department of Bacteriology, School of Medicine, Kagoshima University, Kagoshima, 890 Japan.

Received 11 January 1979; accepted 8 March 1979.

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