High frequency of T lymphocytes committed to interferon-γ transcription upon polyclonal activation in spleen from lymphocytic choriomeningitis virus-infected mice

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Abstract
Splenic T lymphocytes from C3H/HeOur mice infected for 7 days with lymphocytic choriomeningitis virus (LCMV) do not proliferate in response to concanavalin A (Con A). Although the IL-2 gene remained silent after polyclonal activation, the gene encoding the p55 chain of the IL-2 receptor was normally transcribed. These data Indicated that the co-ordinated expression of the unique wave of cytokine and cytokine receptor expression, associated with T cell triggering, did not occur in T lymphocytes from LCMV-infected mice. In a first attempt to characterize the potential of these cells to Initiate the transcription of cytokine genes, we have focused our attention on interferon (IFN)-γ, a cytokine displaying multifocal activities on the immune response. We found that the IFN-γ encoding gene, silent before Con A activation, was transcribed after triggering in normal and LCMV-infected cells. Notably, the level of induction was ∽10-fold higher in LCMV mice than in non-infected control mice. IFN-γ gene was induced in both CD4 and CD8 subsets. Induction was sensitive to cycloheximide addition and thus required de novo protein synthesis. The high level of IFN-γ mRNA transcripts was correlated with a high frequency of cells transcribing this gene. By In situ hybridization we showed that the majority (˜70%) of the splenic T lymphocyte population were positive for IFN-γ mRNAs. A matching increase in IFN-γ protein corresponded to this elevated IFN-γ mRNA level. This observation revealed the existence in LCMV-infected mice of a preponderant peripheral T lymphocyte population which displayed unusual activation and proliferative characteristics.

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