IL‐12‐mediated STAT4 signaling and TCR signal strength cooperate in the induction of CD40L in human and mouse CD8+ T cells. Issue 6 (21st June 2013)

• Record Type: Journal Article
• Authors: Stark, Regina; Hartung, Anett; Zehn, Dietmar; Frentsch, Marco; Thiel, Andreas
• Is Part Of: European journal of immunology. Volume 43:Issue 6(2013:Jun.)
• Page Start: 1511
• Page End: 1517
• Publication Date: 2013-06-21
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201243218
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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.</p> </abstract>