Hematopoietic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model.

We earlier reported that Fischer 344/jcl strain (F344) rats carrying a unique pX gene of human T lymphocyte virus type I (HTLV-I) under control of a rat lymphocyte-specific protein tyrosine kinase (p56lck) type I promoter (lck-pX rats) spontaneously developed epithelial thymomas from the thymic medulla. To investigate the role of bone marrow cells carrying the HTLV-I pX gene in development of thymomas, the bone marrow of normal F344 rats after lethal irradiation was reconstituted by bone marrow mononuclear cells (BMMC) of lck-pX rats. Epithelial thymomas similar to the original thymoma of lck-pX rats frequently developed in the nontransgenic recipients within 5 months after the BMMC transplantation. The thymomas expressed the pX gene, thereby indicating the thymoma cells to be of donor BMMC origin. Since the thymoma also developed in nontransgenic recipients reconstituted by BMMC depleted of adherent cells, it is suggested that nonadherent BMMC of donor lck-pX rats may migrate to and lodge in the thymus of recipient nontransgenic rats then transform into thymoma cells with epithelial characteristics. The thymoma cells were shown to bind to Ulex europaeus Agglutinin-1 (UEA-1) lectin, which binds epithelial cells in the thymic medulla. It was also shown that the nonadherent BMMC fraction used for bone marrow reconstitution contained a number of UEA-1-positive cells. Taken together, UEA-1 positive BMMC may be progenitor cells of the epithelial thymoma. The epithelial thymoma in lck-pX rats sheds light on epithelial cell development in thymic medulla and for oncogenesis of epithelial thymoma in humans.