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Focal Infection and Transformation in Situ of Thymus Cell Subclasses by a Thymotropic Murine Leukemia Virus¹

Department of Radiology [A. D., M. T., M. L., H. S. K.] and Pathology [I. L. W.], Stanford University School of Medicine, Stanford, California 94305

Studies on the maturational lineages of thymic lymphocytes have revealed several subclasses which are distinguishable on the basis of cell size, topographic distribution within the thymus, DNA synthetic and mitotic activity, migratory behavior, and other properties. Strain C57BL/Ka mice were inoculated with radiation leukemia virus at different concentrations, and tissues were removed at defined intervals. Sequential sections were analyzed for virus-specific cytoplasmic antigen expression, for morphological evidence of neoplastic transformation, and for alkaline phosphatase activity. The first detectable sign of MuLV infection was the focal appearance of cytoplasmic viral antigens in cells of the outer thymic cortex, followed by coalescence of such foci and, several weeks later, by the appearance of morphologically transformed and alkaline phosphatase-positive cells, again often focally distributed in the outer thymic cortex. These observations strongly suggest that the large, mitotically active cells of the outer thymic cortex are the principal source of target cells for both productive infection and subsequent lymphoma induction by the virus.

¹ This work was supported by Grants CA 03352 and CA 10372 from the National Cancer Institute, NIH, and by Grants AI-09072 from the NIH and IC5 from the American Cancer Society.

² Faculty Research Awardee of the American Cancer Society and Josiah P. Macy Foundation Scholar, 1974 to 1975.

Received 5/ 6/75. Accepted 8/13/75.