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Activation of human CD141 + and CD1c + dendritic cells in vivo with combined TLR3 and TLR7/8 ligation
Author(s) -
Pearson Frances E,
Chang Karshing,
Minoda Yoshihito,
Rojas Ingrid M Leal,
Haigh Oscar L,
Daraj Ghazal,
Tullett Kirsteen M,
Radford Kristen J
Publication year - 2018
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 - 10.1111/imcb.12009
Subject(s) - cd80 , tlr3 , cytotoxic t cell , cd86 , dendritic cell , plasmacytoid dendritic cell , cd8 , biology , antigen presenting cell , microbiology and biotechnology , t cell , immune system , immunology , cd40 , innate immune system , toll like receptor , in vitro , biochemistry
Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo . We describe a humanized mouse model (hu mice) in which fully functional human CD141 + and CD1c + myeloid and CD123 + plasmacytoid dendritic cells (DC) develop from human cord blood CD34 + cells in immunodeficient mice. CD141 + DC are the human equivalents of murine CD8 + /CD103 + DC which are essential for the induction of tumor‐inhibitory cytotoxic T lymphocyte responses, making them attractive targets to exploit for the development of new cancer immunotherapies. We used CD34 + ‐engrafted NSG‐A2 mice to investigate activation of DC subsets by synthetic dsRNA or ssRNA analogs polyinosinic‐polycytidylic acid/poly I:C and Resiquimod/R848, agonists for TLR3 and TLR8, respectively, both of which are expressed by CD141 + DC. Injection of hu mice with these agonists resulted in upregulation of costimulatory molecules CD80, CD83 and CD86 by CD141 + and CD1c + DC alike, and their combination further enhanced expression of these molecules by both subsets. When combined, poly I:C and R848 enhanced serum levels of key cytokines associated with cross‐presentation and the induction of cytotoxic T lymphocyte responses including IFN‐α, IFN‐β, IL‐12 and CXCL10. These data advocate a combination of poly I:C and R848 TLR agonists as means of activating human DC for immunotherapy.