Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor Alpha Induce Antigen-specific Protection of Mice from Autoimmunity

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2002 Jan 10

PMID 11781361

Citations 157

Authors

Mauritius Menges

Susanne Rossner

Constanze Voigtlander

Heike Schindler

Nicole A Kukutsch

Christian Bogdan

Klaus Erb

Gerold Schuler

Manfred B Lutz

Affiliations

Soon will be listed here.

Abstract

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)-alpha (TNF/DCs) induce antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-alpha 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-alpha results in incompletely matured DCs (semi-mature DCs) which induce peptide-specific IL-10-producing T cells in vivo and prevent EAE.

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