Exp Mol Med.  2010 Aug;42(8):547-554. 10.3858/emm.2010.42.8.055.

The requirement of natural killer T-cells in tolerogenic APCs-mediated suppression of collagen-induced arthritis

• Jung S
• Park YK
• Shin JH
• Lee H
• Kim SY
• Lee GR
• Park SH

• KMID: 1104381
• DOI: http://doi.org/10.3858/emm.2010.42.8.055

Abstract

TGF-beta-induced tolerogenic-antigen presenting cells (Tol-APCs) could induce suppression of autoimmune diseases such as collagen-induced arthritis (CIA) and allergic asthma. In contrast, many studies have shown that NKT cells are involved in the pathogenesis of Th1-mediated autoimmune joint inflammation and Th2-mediated allergic pulmonary inflammation. In this study, we investigated the effect of CD1d-restricted NKT cells in the Tol-APCs-mediated suppression of autoimmune disease using a murine CIA model. When CIA-induced mice were treated with Tol-APCs obtained from CD1d+/- or CD1d-/- mice, unlike CD1d+/- APCs, CD1d-/- Tol-APCs failed to suppress CIA. More specifically, CD1d-/- Tol-APCs failed to suppress the production of inflammatory cytokines and the induction of Th2 responses by antigen-specific CD4 T cells both in vitro and in vivo. Our results demonstrate that the presence of CD1d-restricted NKT cells is critical for the induction of Tol-APCs-mediated suppression of CIA.

Keyword

antigen-presenting cells; antigens; arthritis; CD1d; experimental; immune tolerance; natural killer T-cells

MeSH Terms

Animals
Antibodies/blood
Antibody Formation/immunology
Antibody Specificity/immunology
Antigen-Presenting Cells/*immunology
Antigens, CD1d/immunology
Arthritis, Experimental/blood/*immunology/*prevention & control
Collagen Type II/immunology
Cytokines/blood
Immune Tolerance/*immunology
Inflammation Mediators/blood
Mice
Natural Killer T-Cells/*immunology
Th1 Cells/immunology