title: IL-1 beta enhances CD40 ligand-mediated cytokine secretion by human dendritic cells (DC): a mechanism for T cell-independent DC activation.
abstract: CD40 ligand (CD40L) is a membrane-bound molecule expressed by activated T cells. CD40L potently induces dendritic cell (DC) maturation and IL-12p70 secretion and plays a critical role during T cell priming in the lymph nodes. IFN-gamma and IL-4 are required for CD40L-mediated cytokine secretion, suggesting that T cells are required for optimal CD40L activity. Because CD40L is rapidly up-regulated by non-T cells during inflammation, CD40 stimulation may also be important at the primary infection site. However, a role for T cells at the earliest stages of infection is unclear. The present study demonstrates that the innate immune cell-derived cytokine, IL-1beta, can increase CD40L-induced cytokine secretion by monocyte-derived DC, CD34(+)-derived DC, and peripheral blood DC independently of T cell-derived cytokines. Furthermore, IL-1beta is constitutively produced by monocyte-derived DC and monocytes, and is increased in response to intact Escherichia coli or CD40L, whereas neither CD34(+)-derived DC nor peripheral blood DC produce IL-1beta. Finally, DC activated with CD40L and IL-1beta induce higher levels of IFN-gamma secretion by T cells compared with DC activated with CD40L alone. Therefore, IL-1beta is the first non-T cell-derived cytokine identified that enhances CD40L-mediated activation of DC. The synergy between CD40L and IL-1beta highlights a potent, T cell-independent mechanism for DC activation during the earliest stages of inflammatory responses.
authors.affiliation: Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, Austin and Repatriation Medical Center, Heidelberg, Victoria, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Luft
authors.forename: Michael
authors.initials: M
authors.lastname: Jefford
authors.forename: Petra
authors.initials: P
authors.lastname: Luetjens
authors.forename: Hubertus
authors.initials: H
authors.lastname: Hochrein
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Masterman
authors.forename: Charlie
authors.initials: C
authors.lastname: Maliszewski
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D018952:Antigens, CD34 / Q000096:biosynthesis; D023201:CD40 Ligand / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D018952:Antigens, CD34; D017077:Culture Media, Conditioned; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma