Radiation leukemia virus and X-irradiation induce in C57BL/6 mice two distinct T-cell neoplasms: A growth factor-dependent lymphoma and a growth factor-independent lymphoma

Abstract

Two different classes of neoplastic T cells were isolated from radiation leukemia virus (RadLV)-inoculated and from X-ray-treated C57BL/6 mice. One consisted of growth factor-dependent T-cell lymphoma (FD-TCL) lines which were established from the spleens and thymuses of treated mice within a day of lymphoma detection. FD-TCL cells were often eudiploid and could be grown in pure culture only at high concentrations, or on stromal feeder layers. Non-thymic, factor-dependent TCL cells produced interleukin-2 upon lectin stimulation, and were autostimulatory because they secreted growth factor(s) constitutively. Single cell cloning of FD-TCL cells in semisolid medium required the addition of exogenous conditioned medium. In vivo, FD-TCL cells that were injected intraperitoneally or intravenously homed to the spleen, proliferated in it and killed the injected mice. FD-TCL cells did not produce local tumors at the site of subcutaneous injection. The isolation and study of FD-TCL cells were facilitated by their cultivation on stromal hemotopoietic monolayers in supplemented “lymphocyte medium”, until an autostimulating, self-sustaining concentration of FD-TCL cells was obtained. FD-TCL cells could not be grown from lymphoid tissue of normal, control mice. In contrast, T-cell lymphoma (TCL) lines, which were established from virus-induced thymomas which had been kept in situ for 4–6 weeks after detection, consisted of factor-independent cells that possessed an aneuploid karyotype (in some cases trisomic for chromosome No. 15), and produced local tumors at the site of subcutaneous injection. These cells could be cloned in semisolid medium without addition of exogenous factor(s). The phenotypic markers of TCL cells differed from those of FD-TCL cells, suggesting heterogeneity in the stages of differentiation at which cells can give rise to growth factor-independent (TCL) and to growth factor-dependent (FD-TCL) lines.