학술논문

Escherichia coli Heat-Labile Enterotoxin B Subunit Prevents Autoimmune Arthritis Through Induction of Regulatory CD4+ T Cells
Document Type
Academic Journal
Source
Arthritis & Rheumatism. Jun 01, 2002 46(6):1671-1682
Subject
Language
English
ISSN
0004-3591
Abstract
OBJECTIVE.: The receptor-binding B subunit of Escherichia coli heat-labile enterotoxin (EtxB) is a highly stable, nontoxic protein that is capable of modulating immune responses. This study was conducted to determine whether mucosal administration of EtxB can block collagen-induced arthritis (CIA) and to investigate the mechanisms involved. METHODS.: RESULTS.: Both intranasal and intragastric delivery of EtxB were effective in preventing CIA; a 1-μg dose of EtxB was protective after intranasal administration. A non–receptor-binding mutant of EtxB failed to prevent disease. Intranasal EtxB lowered both the incidence and severity of arthritis when given either at the time of disease induction or 25 days later. EtxB markedly reduced levels of anti-CII IgG2a antibodies and interferon-γ (IFNγ) production while not affecting levels of IgG1, interleukin-4 (IL-4), or IL-10. Disease protection could be transferred by CD4+ T cells from treated mice, an effect that was abrogated upon depletion of the CD25+ population. In addition, CD4+CD25+ T cells from treated mice were able to suppress anti-CII IFNγ production by CII-primed lymph node cells. CONCLUSION.