CD40 signalling induces IL-10-producing, tolerogenic dendritic cells

• Verfasst von: Tüttenberg, Andrea [VerfasserIn]
• Verfasst von: Fondel, Sabine [VerfasserIn]
• Verfasst von: Steinbrink, Kerstin [VerfasserIn]
• Verfasst von: Enk, Alexander [VerfasserIn]
• Verfasst von: Jonuleit, Helmut [VerfasserIn]
• Titel: CD40 signalling induces IL-10-producing, tolerogenic dendritic cells
• Verf.angabe: Andrea Tuettenberg, Sabine Fondel, Kerstin Steinbrink, Alexander H. Enk and Helmut Jonuleit
• Jahr: 2010
• Umfang: 10 S.
• Fussnoten: Erstmals am 15 December 2009 online veröffentlicht ; Gesehen am 19.01.2024
• Titel Quelle: Enthalten in: Experimental dermatology
• Ort Quelle: Oxford : Wiley-Blackwell, 1992
• Jahr Quelle: 2010
• Band/Heft Quelle: 19(2010), 1 vom: Jan., Seite 44-53
• ISSN Quelle: 1600-0625
• DOI: doi:10.1111/j.1600-0625.2009.00975.x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CD40L
• Sach-SW: dendritic cells
• Sach-SW: gene therapy
• Sach-SW: human
• Sach-SW: immunotherapy
• Sach-SW: tolerance
• K10plus-PPN: 187855736X

Abstract

Abstract: Dendritic cells (DC) are potent antigen-presenting cells capable to induce efficient antigen-specific T cell responses in vitro and in vivo. Herein, the maturation process is of great significance, as immature DC (iDC) are known to induce rather regulatory than effector T cell differentiation. This study was designed to characterize the role of the CD40-CD40L pathway for differentiation and function of human DC. Therefore, iDC were stimulated through CD40-CD40L interaction by transduction of DC with adenoviral vectors encoding for CD40L (Ad-CD40L). Resulting DC (CD40L-DC) were analysed concerning their phenotype, cytokine profile and T cell stimulatory capacity. Transduction induced a DC phenotype comparable to stimulation with proinflammatory cytokines as revealed by upregulation of CD83 and the costimulatory molecules CD80 and CD86. Additionally, Ad-CD40L-induced strong production of IL-12p70 not observed in cytokine-matured DC. Surprisingly, the T cell stimulatory capacity was markedly reduced in CD40L-DC. Furthermore, stimulation of CD8+ T cells by peptide-loaded CD40L-DC resulted in a substantial reduction of antigen-specific IFN-γ production. This phenomenon is due to an enhanced IL-10 production of CD40L-DC in DC-T cell coculture as well as a stabilization of the IL-10 receptor expression on activated T cells. These data demonstrate that DC stimulated through CD40-CD40L interaction differentiate into tolerogenic DC with immunomodulatory function.