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Gross Murine Leukemia Virus-induced Alterations in the Thymus of Preleukemic AKR Mice

Laboratory of Nuclear Medicine and Radiation Biology and the Department of Medicine, School of Medicine, Center for the Health Sciences, University of California, Los Angeles, California 90024

AKR mice were inoculated with Gross murine leukemia virus at 3 days of age. Such treatment results in thymic lymphoma in all animals between 8 and 12 weeks of age. Normal AKR mice develop the disease after 28 weeks of age. In this study, virus-treated (AKR-V) and normal (AKR-N) mice were compared. Thymic weights, histology, and cell density as well as functional and mitogen assays of thymocytes and peripheral T-cells were studied. These animals were studied in the fifth week of life, a time of peak thymic size, and when the virus-inoculated mice were not yet leukemic but were a few weeks away from development of their disease.

The AKR-V mice when compared with the normal animals had decreased thymic weights and decreased total thymic cell density due to a loss of cortical cells. Their thymocyte response to the mitogen, phytohemagglutinin, and to alloantigen in mixed lymphocyte culture was increased significantly over that of cells from the AKR-N mouse thymus. Graft-versus-host reactivity of AKR-V thymocytes was also increased. The response to concanavalin A was significantly decreased in the AKR-V thymocytes. Treatment of the animals with cortisone resulted in a thymocyte population from both AKR-V and AKR-N mice with increased reactivity to phytohemagglutinin and concanavalin A as well as an increased responsiveness in the graft versus host reaction. T-cell responses from spleen and lymph node cells in all of the above tests were similar in the two groups, the single exception being that the AKR-V lymph node cells had a significantly higher background of thymidine uptake than did AKR-N cells. These observations suggest that loss in thymic weight of the virus-treated animals is due to a reduction of a subpopulation of cortical cells responsive to concanavalin A. The increased reactivity to phytohemagglutinin and alloantigen in the thymus is considered to be the result of a relative increase in reactive cells produced by the reduction of cortical thymocytes.

¹ Supported by USPHS Grant CA 09120 awarded by the National Cancer Institute.

² Supported by USPHS Grant CA 12386, from the National Cancer Institute, and Contract EY-76-C-03-0012, between the United States Department of Energy and the University of California. To whom requests for reprints should be addressed, at University of California, Los Angeles, Laboratory of Nuclear Medicine and Radiation Biology, Warren Hall, 900 Veteran Avenue, Los Angeles, Calif. 90024.

Received 3/ 2/78. Accepted 11/ 8/78.