Interleukin-2 and antibody to the T cell receptor regulate proliferation of a radiation leukemia virus-transformed T cell lymphoma

In this report, a Radiation leukemia virus-transformed murine T cell lymphoma is described which is dependent on the interleukin-2 (IL-2) growth factor for proliferation under single cell conditions of growth. It was isolated from a C57BL mouse which had been primed with the Radiation leukemia virus-induced thymoma, C6VL/1, and has been shown to be phenotypically and karyotypically distinct from C6VL/1. IL-2 dependency has been stable over many in vitro passages, and this property also serves to distinguish this cell line from C6VL/1. 5C2 constitutively expresses a T cell receptor (TCR) and can respond by increased proliferation to external stimulation with anti-TCR antibody. This antibody acts to stimulate 5C2 growth in the absence of added IL-2. Maximum stimulation was achieved in the presence of a 50-ng/ml concentration of purified antibody. 5C2 has also been shown to produce detectable levels of IL-2 which can be increased by 8- to 16-fold after exposure of cells to anti-TCR antibody. The C6VL/1 T cell lymphoma has served as a control cell line in three experiments since it cannot be stimulated either to increased proliferation or to lymphokine release by this same antibody. However, a 10-ng/ml concentration of anti-TCR antibody was found to inhibit proliferation of both T cell lymphomas when they were cultured under optimal conditions, i.e., in the presence of an IL-2 source for 5C2. The proliferation of both T cell lymphomas appears to be regulated, although in different ways, by the binding of antibody in the vicinity of the TCR complex. While 5C2 is dependent on IL-2 production (and TCR triggering) to proliferate, C6VL/1 replicates independently of any growth factors. Signal transduction through the TCR/T3 complex, together with the subsequent production of growth factors, may be important for driving the proliferation of T cells such as 5C2 at an early stage in oncogenic progression following infection with an RNA tumor virus.