Human CD141+ (BDCA-3)+ Dendritic Cells (DCs) Represent a Unique Myeloid DC Subset That Cross-presents Necrotic Cell Antigens

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2010 May 19

PMID 20479116

Citations 524

Authors

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

Affiliations

Soon will be listed here.

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.

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