CD40 regulates human dendritic cell‐derived IL‐7 production that, in turn, contributes to CD8 + T‐cell antigen‐specific expansion

CD40L (CD154) expressed on activated CD4 + T cells has been shown to provide CD40 + dendritic cells (DCs), a critical signal for establishing CD8 + T‐cell immunity. CD40L–CD40 interaction leads to DC maturation with IL‐12 production and upregulation of various costimulatory molecules. In this study, we show that CD40 engagement provides a unique maturation signal for human monocyte‐derived DCs to upregulate IL‐7 production. Other inducers of DC maturation, such as TLR 4 and TLR 7/8 agonist, fail to induce IL‐7 upregulation. Neutralization of IL‐7 activity in human CD8 + T‐cell cultures stimulated with CMV pp65‐NLV peptide‐pulsed mature DCs (mDCs) leads to a reduction in antigen‐specific CD8 + T‐cell yields suggesting a role for mDC‐derived IL‐7 during T‐cell receptor (TCR) activation. Furthermore, IL‐7 signaling requires a temporal coordination with TCR activation for maximal antigen‐specific T‐cell yields. These results show that CD40 signals regulate DC‐derived IL‐7 production that, in turn, may instruct CD8 + T cells at the time of TCR engagement for survival leading to an increased expansion of antigen‐specific T cells.