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.