Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor α Induce Antigen-specific Protection of Mice from Autoimmunity
By Mauritius Menges, S. Rössner, C. Voigtländer, H. Schindler, N. Kukutsch, C. Bogdan, K. Erb, Gerold Schuler, M. Lutz. Journal of Experimental Medicine, 2002
631 citations recorded by the source corpus.
Mature dendritic cells (DCs) are believed to induce T cell immunity, whereas immature DCs induce T cell tolerance. Here we describe that injections of DCs matured with tumor necrosis factor (TNF)-α (TNF/DCs) induce antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-α induced high levels of major histocompatibility complex class II and costimulatory molecules on DCs, but they remained weak producers of proinflammatory cytokines. One injection of such TNF/DCs pulsed with auto-antigenic peptide ameliorated the disease score of EAE. This could not be observed with immature DCs or DCs matured with lipopolysaccharide (LPS) plus anti-CD40. Three consecutive injections of peptide-pulsed TNF/DCs derived from wild-type led to the induction of peptide-specific predominantly interleukin (IL)-10–producing CD4+ T cells and complete protection from EAE. Blocking of IL-10 in vivo could only partially restore the susceptibility to EAE, suggesting an important but not exclusive role of IL-10 for EAE prevention. Notably, the protection was peptide specific, as TNF/DCs pulsed with unrelated peptide could not prevent EAE. In conclusion, this study describes that stimulation by TNF-α results in incompletely matured DCs (semi-mature DCs) which induce peptide-specific IL-10–producing T cells in vivo and prevent EAE.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/c7704ee27c1d2717bae0ee7e74ae15353ee9ede9
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Citations in the corpus
- Inflammatory signals in dendritic cell activation and the induction of adaptive immunity (2009, background): “In the instances discussed above, DCs provide signal 1 as well as signal 2 yet fail to trigger an immune response (23, 25, 46, 58, 65, 71).”
- Interleukin‐10‐secreting type 1 regulatory T cells in rodents and humans (2006, background): “IL-10 downregulates expression of costimulatory molecules and pro-inflammatory cytokine production by APCs and directly inhibits IL-2 and tumor necrosis factor-a (TNF-a) production by CD4+ T cells (45).”
- Tolerogenic dendritic cells and the quest for transplant tolerance (2007, background): “, and that tolerogenic DCs have been shown to suppress experimental autoimmune diseas”
- The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models (2008, background): “Notably, DC-based vaccination strategies have proven successful in other contexts, as injection of peptide-pulsed mature DCs induced peptide-specific, IL-10-producing CD4 + T cells and protected mice from autoimmune encephalomyeliti”