Mechanisms of hemopoietic and immunological dysfunction induced by lymphocytic choriomeningitis virus

Abstract

Sublethal irradiation (500 R) of C3H mice is followed by a gradual replacement of radiosensitive cells in their spleens by surviving stem cells originating in bone marrow. This compensatory hemopoiesis was quantitated by counting the numbers of stem cell-derived colonies appearing on spleen surfaces, as well as those which grew in vitro after marrow cells, suspended in soft agar, were overlaid onto syngenic mouse embryo fibroblast feeder layers. Compensatory colony formation, both in vivo and in vitro, was severely depressed when mice were infected with lymphocytic choriomeningitis virus (LCMV) 1 day before irradiation, although the induction of virus-specific cytotoxic T cells in their spleens was unimpaired. Without irradiation, mice, acutely infected with LCMV, showed a dramatic reduction in the numbers of specific antibody-forming cells generated in their spleens after priming with sheep erythrocytes during week 1 post-infection, yet the ability of their marrow cells to form colonies in vitro remained normal. Therefore, the basis of immunodepression is distinct from that of defective hemopoiesis since the latter is apparent only when LCMV infection is accompanied by irradiation. However, as discussed, both phenomena may be related to alterations induced within the splenic environment by LCMV.