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 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)-gamma, a cytokine 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. Notably, the level of induction was approximately 10-fold higher in LCMV mice than in non-infected control mice. IFN-gamma 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-gamma mRNA transcripts was correlated with a high frequency of cells transcribing this gene. By in situ hybridization we showed that the majority (approximately 70%) of the splenic T lymphocyte population were positive for IFN-gamma mRNAs. A matching increase in IFN-gamma protein corresponded to this elevated IFN-gamma 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.
Colle
J H
JH
Unité d'Immunophysiologie Moléculaire, Institut Pasteur, Paris, France.
Saron
M F
MF
Shidani
B
B
Lembezat
M P
MP
Truffa-Bachi
P
P
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D007371:Interferon-gamma