Differential capability for phagocytosis of apoptotic and necrotic leukemia cells by human peripheral blood dendritic cell subsets.
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.
Dalgaard
Jakob
J
Institute of Immunology, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo, Norway. jakob.dalgaard@labmed.uio.no
Beckstrøm
Karen J
KJ
Jahnsen
Frode L
FL
Brinchmann
Jan E
JE
D017209:Apoptosis / Q000276:immunology*; D039521:CD11c Antigen / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016895:Culture Media, Serum-Free; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D039641:Integrin beta Chains / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009336:Necrosis / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D039521:CD11c Antigen; D016895:Culture Media, Serum-Free; D039641:Integrin beta Chains; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C084344:integrin beta5; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor