IL-1 beta enhances CD40 ligand-mediated cytokine secretion by human dendritic cells (DC): A mechanism for T cell-independent DC activation
- Author(s)
- Luft, T; Jefford, M; Luetjens, P; Hochrein, H; Masterman, KA; Maliszewski, C; Shortman, K; Cebon, J; Maraskovsky, E;
- Details
- Publication Year 2002-01-15,Volume 168,Issue #2,Page 713-722
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- 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, 11,4 0, 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 cola 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.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- COMBINED IMMUNODEFICIENCY MICE; LEVEL IL-12 PRODUCTION; NECROSIS-FACTOR-ALPHA; IN-VIVO; ENDOTHELIAL-CELLS; IFN-GAMMA; INTERLEUKIN (IL)-12; INTERFERON-GAMMA; SMOOTH-MUSCLE; KILLER-CELL
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Creation Date: 2002-01-15 12:00:00