Pathogenesis of visna. II. Effect of immunosuppression upon early central nervous system lesions.

It was hypothesized that the lesions of visna might represent an immunopathologic process. To test this hypothesis, a 1-month schedule of immunosuppressive treatment was devised, using horse anti-sheep thymocyte serum. In Hampshire sheep, this regime was shown to protect against experimental allergic encephalomyelitis, to inhibit development of tuberculin hypersensitivity, to retard rejection of skin homografts by 3 weeks, and to markedly reduce the number and mitogenic responsiveness of peripheral blood lymphocytes. Two groups of Icelandic sheep received intracerebral inoculations of visna virus, and one group was treated with horse antisheep thymocyte serum supplemented by a short terminal course of cyclophosphamide. Central nervous system lesions were seen in only one of eight suppressed animals at sacrifice 25 days after infection, whereas definite lesions were present in eight of eight infected control animals. The frequency of central nervous system virus isolation was similar in the two groups, indicating that treatment suppressed the cellular proliferative response without preventing the central nervous system phase of infection. Sheep receiving horse antisheep thymocyte serum had a reduced number of virus isolations from peripheral lymphoid tissue, presumably reflecting the lympholytic effect of treatment. These observations are consistent with the immunopathologic hypothesis and suggest several different ways in which suppression could modify the immune response to visna virus.