Immunopathologic alterations of lymphatic tissues of mice infected with lymphocytic choriomeningitis virus. I. Histopathologic findings.

Intraperitoneal infection with strain WE lymphocytic choriomeningitis virus led to illness in all and death in a large proportion of colony-bred NMRI mice. In their lymphoid organs, three distinct types of alterations could be distinguished: destruction of lymphocytes and mononuclear phagocytes, proliferation of lymphocytes, and fibrinoid necrosis of reticular cells and macrophages. After the intraperitoneal inoculation of 10(4) mouse infectious units, in the spleen, infectivity rapidly climbed to a peak on day 3. Virus-specific antigen, as revealed by immunofluorescence method, was first seen 2 to 3 days after infection in spleen and lymph nodes. Macrophages, reticular cells, endothelial cells, and elements of the connective tissues were positive; however, resting lymphocytes did not contain viral antigen. In both organs, immunofluorescence was maximal on day 5 and rapidly diminished thereafter. In the thymus, the concentration of infectious virus rose more slowly and virus-specific antigen, predominantly in cells resembling macrophages but never in lymphocytes, appeared later. In spleen and lymph nodes, first signs of lymphocytolysis were observed on day 3 after infection. Initially, T cells were more affected than B cells, but beginning with day 4 and thereafter, the opposite was true. In parallel with cytolysis, other lymphoid cells began proliferating. On days 4 to 5 after infection, macrophages were found to be activated. At the same time, small foci of fibrinoid necrosis made their appearance. Both lymphocytolysis and lymphoblastoid proliferation were maximal 4 to 5 days after infection, whereas fibrinoid necrosis progressed until day 6. In the thymus, first changes consisting of activation of cortical macrophages were observed on day 6, and these were followed by massive necroses of cortical thymocytes leading to extensive involution of this organ. In surviving animals, regeneration of lymphoid organs commenced around the 9th day.