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

Sarah L. Jongbloed, Andrew J. Kassianos, Kylie J. McDonald, Georgina J. Clark, Xinsheng Ju, Catherine E. Angel, Chun-Jen J. Chen, P. Rod Dunbar, Robert B. Wadley, Varinder Jeet, Annelie J. E. Vulink, Derek N. J. Hart, Kristen J. Radford*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)1247-1260
Number of pages14
JournalJournal of Experimental Medicine
Volume207
Issue number6
DOIs
Publication statusPublished - 7 Jun 2010
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2010. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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