Autoaggressive reactions and leukemia virus infections: interrelated events in their pathogenesis

Leukemia viruses can be activated from within murine hosts by immunological reactions against foreign histocompatibility antigens both during graft versus host reactions (GVHR) and host versus graft reactions (HVGR). Presence of both lymphocyte-mediated graft rejection reactions and immuno suppression appears necessary for maximal virus activation and replication in vitro, although viruses can be activated by mixed lymphocyte reactions (MLR) alone in vitro. During HVGR, viruses are first detectable in lymph nodes draining the graft site, and later reach maximal titers in the spleen. Mice infected with murine leukemia virus (MuLV) as neonates or carrying MuLV secondary to milk transmission (carriers) also develop complex autoaggressive responses. By a sensitive in vitro microcytotoxicity assay, neoplastic or pre-neoplastic thymocytes from carrier mice were found to react vigorously against normal uninfected syngeneic embryonic fibroblasts, whereas they reacted much less vigorously with similarly prepared but MuLV-infected fibroblasts. Thymocytes from uninfected animals did not react with infected or uninfected fibroblasts. Peripheral lymphocytes from carriers reacted against MuLV infected fibroblasts, but not against uninfected fibroblasts, a pattern indistinguishable from deliberately-immunized mice. It is proposed that responses analogous to GVHR are also important in the pathogenesis of leukemia following exogenous leukemia virus infection.