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

doi:10.1084/jem.20092140

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

J Exp Med. 2010 Jun 7;207(6):1247-60. doi: 10.1084/jem.20092140. Epub 2010 May 17.

Authors

Sarah L Jongbloed¹, 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

Affiliation

¹ Dendritic Cell Program, Mater Medical Research Institute, South Brisbane, Queensland 4101, Australia.

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-beta, 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 CD8alpha+ 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens / immunology*
Antigens, CD1 / immunology
Antigens, Surface / metabolism*
CD4-Positive T-Lymphocytes / cytology
CD4-Positive T-Lymphocytes / drug effects
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / immunology
Cell Line
Cross-Priming / drug effects
Cross-Priming / immunology*
Dendritic Cells / cytology
Dendritic Cells / drug effects
Dendritic Cells / immunology*
Humans
Interferon-beta / biosynthesis
Interleukin-12 / biosynthesis
Lymphoid Tissue / cytology
Lymphoid Tissue / drug effects
Lymphoid Tissue / immunology
Myeloid Cells / cytology*
Myeloid Cells / drug effects
Myeloid Cells / immunology
Necrosis / immunology*
Necrosis / pathology
Phosphoproteins / immunology
Poly I-C / pharmacology
Recombinant Proteins / immunology
Th1 Cells / cytology
Th1 Cells / drug effects
Th1 Cells / immunology
Thrombomodulin / metabolism*
Toll-Like Receptor 3 / metabolism
Viral Matrix Proteins / immunology

Substances

Antigens
Antigens, CD1
Antigens, Surface
Phosphoproteins
Recombinant Proteins
THBD protein, human
TLR3 protein, human
Thrombomodulin
Toll-Like Receptor 3
Viral Matrix Proteins
cytomegalovirus matrix protein 65kDa
Interleukin-12
Interferon-beta
Poly I-C