title: Down-modulation of responses to type I IFN upon T cell activation.
abstract: The immunomodulatory role of type I IFNs (IFN-alpha/beta) in shaping T cell responses has been demonstrated, but the direct effects of IFN on T cells are still poorly characterized. Particularly, because IFN exert an antiproliferative activity, it remains elusive how the clonal expansion of effector T cells can paradoxically occur in the event of an infection when large amounts of IFN are produced. To address this issue, we have studied the effects of type I IFN in an in vitro differentiation model of human primary CD4(+) T cells. We found that IFN-alpha treatment of resting naive T cells delayed their entry into the cell cycle after TCR triggering. Conversely, the ongoing expansion of effector T cells was not inhibited by the presence of IFN. Moreover, activated T cells showed a significantly reduced induction of IFN-sensitive genes, as compared with naive precursors, and this decline occurred independently of subset-specific polarization. The residual type I IFN response measured in activated T cells was found sufficient to inhibit replication of the vesicular stomatitis virus. Our data suggest that the activation of T lymphocytes includes regulatory processes that restrain the transcriptional response to IFN and allow the proliferation of effector cells in the presence of this cytokine.
authors.affiliation: Unité de Signalisation des Cytokines and Laboratoire de Immunorégulation, Institut Pasteur, Paris, France.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dondi
authors.forename: Lars
authors.initials: L
authors.lastname: Rogge
authors.forename: Georges
authors.initials: G
authors.lastname: Lutfalla
authors.forename: Gilles
authors.initials: G
authors.lastname: Uzé
authors.forename: Sandra
authors.initials: S
authors.lastname: Pellegrini
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D007399:Interphase / Q000276:immunology; D053613:Janus Kinase 1; D008213:Lymphocyte Activation / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D007370:Interferon Type I; D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D016899:Interferon-beta; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1