Kinetic analysis of Ly‐6 gene induction in a T lymphoma by interferons and interleukin 1, and demonstration of Ly‐6 inducibility in diverse cell types

The Ly‐6 locus contains multiple genes encoding cell surface proteins, two of which, when cross‐linked by antibodies, effect antigen‐independent activation of T lymphocytes. In this study, cDNA for Ly‐6‐encoded antigens have been used as probes to examine RNA from various tissues and transformed cell lines for constitutive levels of Ly‐6 RNA expression. Analyses of RNA prepared from several different tissues revealed a high level of expression of Ly‐6 RNA in kidney, spleen, heart and thymus, with a more moderate level of expression in liver, brain and lung tissue cells. A survey of various cell lines demonstrated the presence of Ly‐6 RNA in many, but not all T lymphocytic cell lines, in L cells, the Meth A fibrosarcoma, in the TCMK kidney cell line, and in the Neuro‐2a neuroblastoma. We also evaluated the expression of Ly‐6 RNA in cells after treatments with interferons (IFN) and interleukin 1 (IL 1). Treatment of lymphoid cells with IFN (α/β and γ), known to increase cell surface Ly‐6 antigen expression in normal T cells, was correlated with increases in Ly‐6 RNA levels. Increases in levels of RNA correlated with increases in levels of the Ly‐6A/E or Ly‐6C antigens. Several T lymphoid cell lines exhibiting Ly‐6 RNA inducibility by IFN were similarly inducible with IL 1. Kinetic experiments using one such line, (YAC‐1), showed that the induction of Ly‐6 RNA mediated by IFN‐α/β occurred rapidly (within 4 h), while the induction by IL 1 required relatively more time (∼ 8 h). Although the actions of IFN‐α/β were not blocked by cycloheximide, the presence of this protein synthesis inhibitor significantly attenuated the effects of IL 1 and IFN‐γ on Ly‐6 RNA transcription. Induction by IFN‐γ as well as IL 1 could be blocked completely by co‐culture with anti‐IFN‐γ, implicating IFN‐γ as a mediator of the induction by IL 1.