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CD40 regulates human dendritic cell‐derived IL‐7 production that, in turn, contributes to CD8 + T‐cell antigen‐specific expansion
Author(s) -
Carreno Beatriz M,
BeckerHapak Michelle,
Linette Gerald P
Publication year - 2009
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2008.80
Subject(s) - cd40 , microbiology and biotechnology , t cell , cd8 , downregulation and upregulation , t cell receptor , cd154 , antigen presenting cell , antigen , dendritic cell , cytotoxic t cell , biology , antigen presentation , chemistry , immunology , immune system , biochemistry , in vitro , gene
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.