CD137 ligand signaling induces human monocyte to dendritic cell differentiation.
The ligand for CD137 (4-1BB) is expressed on peripheral human monocytes and delivers a potent activating signal via reverse signaling. Here we show that treatment of monocytes with a recombinant CD137 protein that induces reverse signaling through CD137 ligand reduces typical macrophage characteristics such as phagocytosis, oxidative burst and CD14 expression; however, typical DC characteristics including endocytosis, costimulatory molecule expression and the ability to stimulate proliferation of naïve T cells are induced. CD137-generated DC do not express DC-SIGN, CD1a or IL-12 and secrete less IL-10 than classical DC. CD137-generated DC are mature, and addition of LPS+IFN-gamma does not enhance their T-cell-stimulatory capacity. This indicates that CD137 as a sole factor is sufficient to induce development to mature DC, making stimulation of CD137 ligand the most simple protocol to generate mature DC. CD137-generated DC are more potent in inducing T-cell proliferation than classical DC. They inhibit development of Treg cells but induce T-cell expression of perforin, IFN-gamma, IL-13 and IL-17. These data demonstrate that CD137 as a single factor is sufficient to induce differentiation of peripheral monocytes to mature inflammatory DC that have a more potent T-cell-stimulatory capacity than classical DC.
Kwajah M M
Shaqireen
S
Department of Physiology and Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Schwarz
Herbert
H
D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D054353:Perforin / Q000096:biosynthesis / Q000235:genetics; D010587:Phagocytosis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000494:pharmacology*
D000943:Antigens, Differentiation; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D054353:Perforin