IL -12-mediated STAT 4 signaling and TCR signal strength cooperate in the induction of CD 40 L in human and mouse CD 8 super(+) T cells

CD 40 L 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. CD 4 super(+) T cells have been regarded as the major T -cell subset that expresses CD 40 L upon cognate activation; however, we demonstrate here that a putative CD 8 super(+) helper T -cell subset expressing CD 40 L is induced in human and murine CD 8 super(+) T cells in vitro and in mice immunized with antigen-pulsed dendritic cells. IL -12 and STAT 4-mediated signaling was the major instructive cytokine signal boosting the ability of CD 8 super(+) T cells to express CD 40 L both in vitro and in vivo. Additionally, TCR signaling strength modulated CD 40 L expression in CD 8 super(+) T cells after primary differentiation in vitro as well as in vivo. The induction of CD 40 L in CD 8 super(+) T cells regulated by IL -12 and TCR signaling may enable CD 8 super(+) T cells to respond autonomously of CD 4 super(+) 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 APC s.