title: IL-12-mediated STAT4 signaling and TCR signal strength cooperate in the induction of CD40L in human and mouse CD8+ T cells.
abstract: CD40L is one of the key molecules bridging the activation of specific T cells and the maturation of professional and nonprofessional antigen-presenting cells including B cells. CD4(+) T cells have been regarded as the major T-cell subset that expresses CD40L upon cognate activation; however, we demonstrate here that a putative CD8(+) helper T-cell subset expressing CD40L is induced in human and murine CD8(+) T cells in vitro and in mice immunized with antigen-pulsed dendritic cells. IL-12 and STAT4-mediated signaling was the major instructive cytokine signal boosting the ability of CD8(+) T cells to express CD40L both in vitro and in vivo. Additionally, TCR signaling strength modulated CD40L expression in CD8(+) T cells after primary differentiation in vitro as well as in vivo. The induction of CD40L in CD8(+) T cells regulated by IL-12 and TCR signaling may enable CD8(+) T cells to respond autonomously of CD4(+) T cells. Thus, we propose that under proinflammatory conditions, a self-sustaining positive feedback loop could facilitate the efficient priming of T cells stimulated by high affinity peptide displaying APCs.
authors.affiliation: Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Berlin, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Stark
authors.forename: Anett
authors.initials: A
authors.lastname: Hartung
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.forename: Marco
authors.initials: M
authors.lastname: Frentsch
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002478:Cells, Cultured; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020239:Receptor Cross-Talk; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050797:STAT4 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D011948:Receptors, Antigen, T-Cell; D050797:STAT4 Transcription Factor; D023201:CD40 Ligand; D018664:Interleukin-12