Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens

By Sarah L. Jongbloed, Andrew J. Kassianos, Kylie J. McDonald, G. Clark, X. Ju, C. E. Angel, Chun-Jen J. Chen, P. Dunbar, R. Wadley, Varinder Jeet and 3 more. Journal of Experimental Medicine, 2010

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The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141+ DC subset. CD141+ DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-β, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c+ DC subset. Polyinosine-polycytidylic acid (poly I:C)–activated CD141+ DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8+ cytotoxic T lymphocytes than poly I:C–activated CD1c+ DCs. Importantly, CD141+ DCs, but not CD1c+ DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141+ DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8α+ DC subset. The data demonstrate a role for CD141+ DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/9b7b4975ae6071b432577694b6105b10a85f9411

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Citations in the corpus

Vaccine Adjuvants: Putting Innate Immunity to Work (2010, background): “Moreover, mouse (Bedoui et al., 2009; Schulz et al., 2005) or human (Jongbloed et al., 2010; Poulin et al., 2010) DC subsets specialized for cross-presentation show increased CD8+ T cell immunity when Poly IC is used to activate cells through TLR3.”
Dendritic-cell-based therapeutic cancer vaccines. (2013, background): “, 2013) and, when activated with poly I:C, efficiently cross-primeCD8Tcells (Bachemet al., 2010;Crozat et al., 2010; Haniffa et al., 2012; Jongbloed et al., 2010; Lauterbach et al., 2010; Mittag et al., 2011; Poulin et al., 2010).”
Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic Cells (2012, background): “CD8+ T cells usually occurs in the context of a Th1 cell response reinforced by IL-12 production (Reis e Sousa et al., 1997).”
Cancer immunotherapy via dendritic cells (2012, positive): “CLEC9A-expressing CD141 DCs isolated from human lymph nodes were able to cross-present long peptides (requiring processing) of melanoma-tissue-derived antigen (MART-1) to T cell lines [46], whereas blood DCs can cross-present when activated via Toll-like receptor ligands [18, 19].”
Expansion and activation of CD103+ dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition (2016, positive): “…CD103+ DCs, human CD141+ DCs express IRF8 and high levels of FLT3 and TLR3, and pIC activation of human CD141+ cells leads to the upregula- tion of PD-L1 (Bogunovic et al., 2011) and to their increased cross-priming of CD8+ T cells (Crozat et al., 2010; Jongbloed et al., 2010; Poulin et al., 2010).”