Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets

Abstract

CD11c+ dendritic cells (DC) and plasmacytoid DC (PDC) are the two major DC subsets in human peripheral blood. For the purpose of immunotherapy with DC, it is important to investigate the phagocytosis of killed tumor cells by different DC subsets. Using immature monocyte-derived DC (iMoDC) as reference, we have compared the ability of CD11c+ DC and PDC to phagocytose apoptotic and necrotic K562 leukemia cells. Freshly isolated CD11c+ DC phagocytosed apoptotic and necrotic K562 cells, whereas PDC did not show any evidence of uptake of dead cells. Blocking studies showed that CD36 is importantly involved in uptake of apoptotic and necrotic material. CD91 and CD11c were also involved. In addition, we found that beta5 integrin was expressed on CD11c+ DC but not in its classical association with alphaV. Uptake of apoptotic K562 cells by CD11c+ DC was increased following incubation with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4, alone or in combination with transforming growth factor-beta1, to levels comparable with those observed for iMoDC. Phagocytosis of dead cellular material by the GM-CSF/IL-4-treated CD11c+ DC was largely restricted to a subset expressing low levels of human leukocyte antigen-DR and CD83. Thus, the relationship between phagocytosis of antigenic material and expression of maturation-related cell-surface molecules is similar for CD11c+ DC and MoDC. We conclude that CD11c+ DC in peripheral blood are precursor cells, which under the influence of cytokines, differentiate to cells with DC phenotype and function.

Human Plasmacytoid Dendritic Cells Phagocytose, Process, and Present Exogenous Particulate Antigen

“…First,the composition of the studied particulates(apoptotic cells, beads, bacteria, or PLGA microparticles) is diverse and uptake might require different receptors and uptake mechanisms, some of which may not be exploited by pDCs. Furthermore, some studies compared the phagocytic capacity of pDCs to that of moDCs and found that pDCs showed very little to no uptake compared with moDCs (3,14,18). We also found that moDCs were superior to pDCs in phagocytosing particulate Ag, notwithstanding that almost all pDCs engulfed particles.…”

“…In this study, we investigated whether pDCs can play a role in immune responses against exogenous particulates. Up to now, it was highly controversial whether pDCs are able to respond to stimuli entrapped in particle-like structures (3,8,9,14,(16)(17)(18)(19). We demonstrate that pDCs are clearly capable of phagocytosing Ag entrapped within PLGA microparticles and subsequent processing of the encapsulated Ag.…”

“…Although some studies show that pDCs phagocytose apoptotic cells (16,17), several report that pDCs hardly take up particulates, such as apoptotic cells (18), latex beads (17,19), zymosan granules (14), or extracellular bacteria (3). Human pDCs have been shown to prime functional T cell responses on phagocytosis of apoptotic debris (16).…”

Both Langerhans cells and interstitial DC cross‐present melanoma antigens and efficiently activate antigen‐specific CTL

“…The ability of human DC to capture necrotic/ apoptotic cells has been demonstrated with either MDDC [21,31,45,46] or blood mDC [47]. Mouse LC were shown to phagocytose many types of particles [48].…”

Mouse dendritic cells matured by ingestion of apoptotic blebs induce T cells to produce interleukin‐17

“…Notably, another type of DC, the plasmacytoid DC (PDC), responds specifically to RNA/DNAcontaining immune complexes by producing the type I interferon interferon-␣ (IFN␣), which seems crucially involved in the pathogenesis of SLE (27,28). However, ingestion of apoptotic cells by PDCs is unlikely to occur (29).…”