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

TLDR

Characterizing human dendritic cell subsets is essential for designing new vaccines. This study provides the first detailed functional analysis of the human CD141+ dendritic cell subset. CD141+ DCs were isolated from lymph nodes, bone marrow, tonsil, and blood, with blood yielding the most highly purified cells for analysis. CD141+ DCs exhibit high TLR3, IL‑12p70, and IFN‑β production, superior Th1 induction, and markedly better cross‑presentation of soluble protein and viral antigens from necrotic cells compared with CD1c+ DCs, establishing them as a distinct human DC subset analogous to mouse CD8α+ DCs and a promising target for vaccines against cancers and viral infections.

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.