A Comparative Study of the T Cell Stimulatory and Polarizing Capacity of Human Primary Blood Dendritic Cell Subsets.

Simone P Sittig,Carl G Figdor,Jorieke Weiden,Jurjen Tel,Gerty Schreibelt,Annette E Sköld,Ghaith Bakdash,I Jolanda M De Vries

doi:10.1155/2016/3605643

Simone P Sittig, Carl G Figdor + Show 6 more

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https://doi.org/10.1155/2016/3605643

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Abstract

Dendritic cells (DCs) are central players of immune responses; they become activated upon infection or inflammation and migrate to lymph nodes, where they can initiate an antigen-specific immune response by activating naive T cells. Two major types of naturally occurring DCs circulate in peripheral blood, namely, myeloid and plasmacytoid DCs (pDCs). Myeloid DCs (mDCs) can be subdivided based on the expression of either CD1c or CD141. These human DC subsets differ in surface marker expression, Toll-like receptor (TLR) repertoire, and transcriptional profile, suggesting functional differences between them. Here, we directly compared the capacity of human blood mDCs and pDCs to activate and polarize CD4+ T cells. CD141+ mDCs show an overall more mature phenotype over CD1c+ mDC and pDCs; they produce less IL-10 and more IL-12 than CD1c+ mDCs. Despite these differences, all subsets can induce the production of IFN-γ in naive CD4+ T cells. CD1c+ and CD141+ mDCs especially induce a strong T helper 1 profile. Importantly, naive CD4+ T cells are not polarized towards regulatory T cells by any subset. These findings further establish all three human blood DCs—despite their differences—as promising candidates for immunostimulatory effectors in cancer immunotherapy.

Highlights

Dendritic cells (DCs) are professional antigen-presenting cells that possess the unique capacity to activate and prime naive CD4+ and CD8+ T cells [1]
Plasmacytoid DCs were stimulated with R848 or CpG and IL-3 used for the control to secure plasmacytoid DCs (pDCs) survival
On CD1c+ Myeloid dendritic cell pDC (mDC), the costimulatory molecule CD86 was already highly expressed after overnight culture in medium alone; on CD141+ mDCs, this holds true for the expression of both CD80 and CD86 (Figure 1(b))

Summary

Introduction

Dendritic cells (DCs) are professional antigen-presenting cells that possess the unique capacity to activate and prime naive CD4+ and CD8+ T cells [1]. Plasmacytoid DCs are key effectors of innate immune responses due to their capacity to produce large amounts of type I IFNs in response to bacterial or viral infections; this production can be induced by TLR agonists such as R848 and oligodeoxynucleotides class C (CpG) [8, 9]. Besides their role in the innate immune system, pDCs participate in priming T helper (Th) cells, depending on the stimulus they receive (summarized in [9]). For both pDCs and mDCs, it has been shown that they induce proliferation in an allogeneic setting and that they can crosspresent exogenous antigens to prime CD8+ T cells [10,11,12,13,14,15,16]

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