HIGH-FREQUENCY OF T-LYMPHOCYTES COMMITTED TO INTERFERON-GAMMA TRANSCRIPTION UPON POLYCLONAL ACTIVATION IN SPLEEN FROM LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INFECTED MICE

Splenic T lymphocytes from C3H/HeOur mice infected for 7 days with lym phocytic choriomeningitiS virus (LCMV) do not proliferate in response to concanavalin A (Con A). Although the IL-2 gene remained silent afte r polyclonal activation, the gene encoding the p55 chain of the IL-2 r eceptor was normally transcribed. These data indicated that the co-ord inated expression of the unique wave of cytokine and cytokine receptor expression, associated with T cell triggering, did not occur in T lym phocytes from LCMV-infected mice. In a first attempt to characterize t he potential of these cells to initiate the transcription of cytokine genes, we have focused our attention on interferon (IFN)-gamma, a cyto kine displaying multifocal activities on the immune response. We found that the IFN-gamma encoding gene, silent before Con A activation, was transcribed after triggering in normal and LCMV-infected cells. Notab ly, the level of induction was approximately 10-fold higher in LCMV mi ce than in non-infected control mice. IFN-gamma gene was induced in bo th CD4 and CD8 subsets. Induction was sensitive to cycloheximide addit ion and thus required de novo protein synthesis. The high level of IFN -gamma mRNA transcripts was correlated with a high frequency of cells transcribing this gene. By in situ hybridization we showed that the ma jority (approximately 70%) of the splenic T lymphocyte population were positive for IFN-gamma mRNAs. A matching increase in IFN-gamma protei n corresponded to this elevated IFN-gamma mRNA level. This observation revealed the existence in LCMV-infected mice of a preponderant periph eral T lymphocyte population which displayed unusual activation and pr oliferative characteristics.