Effects of Anti-Thymocyte Serum on Lymphocytic Choriomeningitis (LCM) Virus Infection in Mice

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Abstract
The role of cellular immunity in LCM virus pathogenesis in mice was examined, using rabbit anti-mouse thymocyte (RAMT) serum to inhibit host response. Three to 4 week old ICR mice of both sexes were divided into 8 groups. All were inoculated intracerebrally with 1000 LD50 of Armstrong E-350 strain of LCM virus on day 0. Varying dosage schedules of RAMT serum and normal rabbit serum were given to the different groups, both before and after virus inoculation, and all groups were observed for clinical and histologic signs of infection. Normal rabbit serum had no effect on the development of LCM infection, which was uniformly fatal in controls between days +5 and +8. Varying RAMT serum treatment schedules, however, significantly modified the course of infection. Clinical and histologic signs of infection were absent so long as therapy was regularly maintained, although high brain and blood virus titers persisted. Anti-LCM antibody production proceeded in RAMT serum treated animals, despite suppression of cellular responsiveness. Severity of the host response to the virus following discontinuation of prolonged therapy was also reduced. Treatment in the early period of incubation (days 0, +1, +2) resulted in a longer median prolongation of life than later treatment (days +3, +4, +5). The proposed mechanisms of action of RAMT serum, and the importance of thymus-dependent cellular responsiveness in LCM infection, are discussed.