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Influence of Genotype and the Organ of Origin on the Subtype of T-Cell in Moloney Lymphomas Induced by Transfer of Preleukemic Cells from Athymic and Thymus-bearing Mice¹

Department of Virology, Karolinska Institutet, S-105 21 Stockholm, Sweden [B. Å., I. P., E-M. F.]; Department of Tumor Pathology, Karolinska Hospital, S-104 01 Stockholm, Sweden [L. S.]; Department of Tumor Biology, Karolinska Institutet, S-104 01 Stockholm, Sweden [I. P., F. W.]; Department of Microbiology and Immunology, Kirksville College of Osteopathic Medicine, Kirksville, Missouri 63501 [D. I.]; and Department of Microbiology, The University of Texas Medical Branch, Galveston, Texas 77550 [J. C.]

Thymus, spleen, and bone marrow of 1-month-old neonatally Moloney murine leukemia virus-inoculated mice have been transferred to 400-R-irradiated syngeneic recipients of the opposite sex. The donor or recipient origin of T-cell lymphomas arising in the host animal was identified by the sex chromosome marker.

Spleen and bone marrow of athymic BALB-nu/nu mice contain cells with the potential to develop into T-cell lymphomas upon transfer to thymus-bearing BALB/c recipients. Such lymphomas arise from at least two subsets of T-cells, one terminal deoxynucleotidyl transferase (TdT) positive and the other 20-hydroxysteroid dehydrogenase positive. The enzyme-negative precursor T-cells from the BALB-nu/nu spleen and bone marrow can thus mature to enzyme-positive cells and give rise to lymphoma in the thymus-bearing recipient. Preleukemic spleen and bone marrow, but not thymus, from CBA and BALB/c mice regularly contained cells with the potential to develop lymphoma. The subset of T-cell involved was influenced by the genotype since lymphomas arising after the transfer of CBA and BALB/c spleens were TdT positive and 20-hydroxysteroid dehydrogenase positive, respectively. In thymus-bearing mice, but not in nude mice, the transfer of preleukemic spleen cells gave lymphomas earlier than did transfer of bone marrow cells. This suggests that the more mature lymphoid cell population in the spleen of thymusbearing mice may allow leukemic transformation to occur more rapidly than do the less mature cells in the bone marrow.

In one-third of the cases, the virus produced by the preleukemic cells transferred induced new lymphomas involving recipient host cells. These de novo-induced lymphomas were all TdT positive. We suggest that leukemic transformation of TdT-positive cells may occur through a different mechanism than does transformation of cells bearing the 20-hydroxysteroid dehydrogenase marker.

¹ This investigation was supported by the Swedish Cancer Society, the Swedish Society of Medical Sciences, and the National Science Foundation (Grant 7922943).

² To whom requests for reprints should be addressed.

Received 7/ 2/84. Accepted 10/30/84.