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Title: IL-1 beta enhances CD40 ligand-mediated cytokine secretion by human dendritic cells (DC): a mechanism for T cell-independent DC activation.
Austin Authors: Luft, Thomas;Jefford, Michael;Luetjens, Petra;Hochrein, Hubertus;Masterman, Kelly-Anne;Maliszewski, Charlie;Shortman, Ken;Cebon, Jonathan S ;Maraskovsky, Eugene
Affiliation: Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, Austin and Repatriation Medical Center, Heidelberg, Victoria, Australia
Issue Date: 15-Jan-2002
Publication information: Journal of Immunology (baltimore, Md. : 1950); 168(2): 713-22
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.
Gov't Doc #: 11777965
Journal: Journal of Immunology (Baltimore, Md. : 1950)
Type: Journal Article
Subjects: Adjuvants, Immunologic.physiology
Antigens, CD34.biosynthesis
CD40 Ligand.pharmacology.physiology
Cell Differentiation.immunology
Cells, Cultured
Chemotaxis, Leukocyte.immunology
Culture Media, Conditioned.pharmacology
Dendritic Cells.cytology.immunology.secretion
Lymphocyte Activation
Lymphocyte Culture Test, Mixed
Receptors, Interleukin-6.physiology
Tumor Necrosis Factor-alpha.pharmacology
Appears in Collections:Journal articles

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