Leukemogenesis by an Endogenous Virus Isolated From the CFW Mouse. II. Early Effects of Virus on Thymus Gland and Bone Marrow Cell Populations2

Abstract

The early effects of a highly leukemogenic and rapidly acting murine leukemia virus (DMBALV) on the thymus glands of CFW/D mice were investigated. Infection of 1-day-old Intrarenal thymic grafts markedly stimulated the division of cells derived from the graft. At 30 days post grafting, when all dividing cells in control grafts were derived from the host, the DMBALV-infected grafts were composed of dividing cells originating exclusively from the graft. Further, the modal chromosome number for cells from the virus-infected grafts was 41, characteristic of virus-induced thymic lymphomas. The DMBALV-infected grafts did not undergo thymus involution, and all thymic lymphomas were composed of cells derived from the graft. If virus infection of the grafts was delayed for 7 days post grafting, the repopulation of the grafts by cells derived from the host did occur and dividing cells of host origin were detected earlier in virus-infected grafts than in control grafts. All thymic lymphomas induced by this protocol were derived exclusively from the host. Reconstruction experiments with the use of lethally irradiated recipients protected with normal bone marrow indicated that target cells for the viral induction of thymic lymphomas are bone marrow derived. These results indicate that the thymus glands in newborns contain bone marrow-derived cells that are transiently susceptible to viral infection and neoplastic conversion. Thymic lymphomas arise as a result of the proliferation of these cells. Thymic injury and/or repopulation of the thymic grafts by cells derived from the host are not necessary prerequisites for tumor induction. Attempts to infect normal thymocytes by cocultivation on thymic epithelial reticulum monolayers derived from DMBALV-induced thymic lymphomas were unsuccessful. In vivo injection of cocultured thymocytes resulted in the appearance of tumors, but karyotypic analysis of all such tumors (by means of a marker chromosome) indicated that the tumors were composed of cells originating from the tumors from which the epithelial reticulum monolayers were derived.