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.
Carreno
Beatriz M
BM
Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA. bcarreno@wustl.edu
Becker-Hapak
Michelle
M
Linette
Gerald P
GP
D019013:CD40 Antigens / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation
D019013:CD40 Antigens; D015851:Interleukin-7