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Published online before print February 22, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1204711

Received for publication December 8, 2004.

Accepted for publication January 21, 2005.

Article

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

Jakob Dalgaard ^*@, Karen J. Beckstrøm ^*, Frode L. Jahnsen , and Jan E. Brinchmann ^*

*Institute of Immunology and Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, Rikshospitalet University Hospital and University of Oslo, Norway

^@ To whom correspondence should be addressed. E-mail: jakob.dalgaard{at}labmed.uio.no.

	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 5 integrin was expressed on CD11c⁺ DC but not in its classical association with V. 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-1, 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.

Key Words: CD11c⁺ • PDC • MoDC • uptake • CD36

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