IL-2 independent growth and cytotoxicity of herpesvirus saimiri-infected human CD8 cells and involvement of two open reading frame sequences of the virus.

Herpesvirus saimiri is a primate tumor virus and induces acute T cell lymphomas and leukemias in New World monkeys and rabbits. We show in this report that infection of human peripheral white blood cells with a group C strain 484-77 results in selective expansion of CD8 lymphocytes with strong cytotoxic activity and these cells do not require interleukin-2 (IL-2) for growth. Infected cell cultures, termed herpesvirus-activated killer (HAK) cells, have been continuously maintained for several months in tissue culture and these HAK cells contain multiple copies of stable circular viral episomes. The growth and cytotoxicity of HAK cells was found independent of IL-2. Analysis of deletion mutant infected cells suggests that at least two open reading frame sequences of a bicistronic mRNA encoded by the viral genome is involved in controlling IL-2 independence. This model could facilitate studies on growth regulation of human cytotoxic T cells that are important effector cells in immune responses against infectious diseases and cancer and should help us to elucidate the mechanism of transformation by H. saimiri oncogenes.