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

BM Carreno, M Becker‐Hapak… - Immunology and cell …, 2009 - Wiley Online Library
BM Carreno, M Becker‐Hapak, GP Linette
Immunology and cell biology, 2009Wiley Online Library
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 …
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.
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