Effect of interleukin-7 on the in vitro development and maturation of monocyte derived human dendritic cells.
We have compared the cell phenotype and functional properties of monocyte/macrophage derived dendritic cells (DCs) obtained by culture of human adherent peripheral blood mononuclear cells (PBMCs) in medium containing granulocyte macrophage colony stimulating factor (GM-CSF) either alone (GM-CSF-DCs), or in combination with interleukin (IL)-4 (IL4-DCs) or IL-7 (IL7-DCs). The cell surface phenotype of GM-CSF-DCs and IL-7-DCs was characterized by a high expression of major histocompatibility complex (MHC) class I and II, CD80, CD86 and CD40. In contrast to 'classical' IL-4-DCs, these two types of DCs expressed CD14 and a CD21-like molecule detected by two out of four CD21-specific monoclonal antibodies (MoAb) tested. The same pattern of reactivity with CD21 specific antibodies was observed in freshly isolated adherent PBMCs but not in B lymphocytes. This reactivity was upregulated by IL-7 in a dose dependent manner. Lipopolysaccharide (LPS) treatment induced the upregulation of CD40, CD80, CD86 and the T-cell stimulatory capacity in IL-4-DCs and, to a lesser extent, in the IL-7-DCs whereas GM-CSF-DCs responded very poorly to such treatment. Our data indicate that, together with GM-CSF, the IL-7 drives macrophage precursors to a differentiation stage that is close to but distinct from the phenotype of IL-4-DCs. Comparison of DC development in the presence of IL-7 or IL-4 may help in dissecting signalling pathways that regulate the expression of functionally relevant DC markers.
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Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Masucci
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MG
Levitsky
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D015703:Antigens, CD / Q000096:biosynthesis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation
D015703:Antigens, CD; D004338:Drug Combinations; D015395:Histocompatibility Antigens Class I; D015851:Interleukin-7; D011994:Recombinant Proteins; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor