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Changes Induced by Lactic Dehydrogenase Virus in Thymus and Thymus-Dependent Areas of Lymphatic Tissue¹

From the Carcinogenesis Program, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee

Abstract

To examine the effects of lactic dehydrogenase virus (LDV) on stromal and parenchymal cells of the thymus and thymus-dependent regions of lymphatic tissue, virus was injected either i.p. or intrathymically into male BALB/c mice that had been either thymectomized and irradiated, adrenalectomized or not treated. Serum lactate dehydrogenase activity was determined, and the spleen, mesenteric lymph node and thymus were weighed and prepared for histologic and ultrastructural examination.

The principal events of the infection process took place during the first 48 hr after infection and were: 1) virus particles, seen in ultrastructure, consistently associated with the plasma membrane of phagocytic cells of the reticulum, with some virusmembrane configurations suggesting replication by budding from these cells; 2) eventual degeneration of these phagocytic reticular cells; 3) cytotoxic degeneration of thymus-derived lymphocytes and their subsequent phagocytosis by macrophages. The cortex of the thymus was markedly depleted of lymphocytes by 4 days after intrathymic virus injection, as opposed to minimal depletion after i.p. injection. Virus particles were directly associated with the stromal cells but not with the thymusderived lymphocytes, indicating that the latter cytopathic effect was mediated by some intermediate soluble factor. This response also occurred in adrenalectomized animals that were inoculated with LDV, indicating that the intermediate factor is not an adrenal cortical steroid.

Serum lactate dehydrogenase activity increased sharply after i.p. or intrathymic injection of the virus into otherwise untreated animals; it then declined slightly and remained constant throughout the remainder of the experiment. Initially the spleen weights increased, whereas thymus weights decreased, although in thymectomized-irradiated animals the increase in spleen weight was 60% greater, and the serum lactate dehydrogenase activity increased to a peak in half of the time of the controls.

Footnotes

¹ This research was supported jointly by the National Cancer Institute and the United States Atomic Energy Commission under contract with the Union Carbide Corporation.

² Participant in the Great Lakes Colleges Association Program, Denison University, Granville, Ohio.