IL‐10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells

• Published in: International immunology 2004-02, Vol.16 (2), p.249-256
• Main Authors: Zhang, Xingmin, Koldzic, Djordje N., Izikson, Leonid, Reddy, Jayagopala, Nazareno, Remedios F., Sakaguchi, Shimon, Kuchroo, Vijay K., Weiner, Howard L.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - immunology; CD25+CD4+ regulatory T cells; CD4 Antigens - immunology; Central Nervous System - immunology; Central Nervous System - pathology; Encephalomyelitis, Autoimmune, Experimental - immunology; experimental autoimmune encephalomyelitis; Female; IL‐10; Inflammation - immunology; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Interleukin-10 - genetics; Interleukin-10 - immunology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Mice; Mice, Knockout; Myelin Proteolipid Protein - immunology; Myelin Proteolipid Protein - pharmacology; Peptide Fragments - immunology; Peptide Fragments - pharmacology; Receptors, Cytokine - metabolism; Receptors, Interleukin-2 - immunology; T-Lymphocytes, Regulatory - immunology
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/dxh029

CD25+CD4+ regulatory T cells inhibit the activation of autoreactive T cells in vitro and in vivo, and suppress organ‐specific autoimmune diseases. The mechanism of CD25+CD4+ T cells in the regulation of experimental autoimmune encephalomyelitis (EAE) is poorly understood. To assess the role of CD25+CD4+ T cells in EAE, SJL mice were immunized with myelin proteolipid protein (PLP)139–151 to develop EAE and were treated with anti‐CD25 mAb. Treatment with anti‐CD25 antibody following immunization resulted in a significant enhancement of EAE disease severity and mortality. There was increased inflammation in the central nervous system (CNS) of anti‐CD25 mAb‐treated mice. Anti‐CD25 antibody treatment caused a decrease in the percentage of CD25+CD4+ T cells in blood, peripheral lymph node (LN) and spleen associated with increased production of IFN‐γ and a decrease in IL‐10 production by LN cells stimulated with PLP130–151 in vitro. In addition, transfer of CD25+CD4+ regulatory T cells from naive SJL mice decreased the severity of active EAE. In vitro, anti‐CD3‐stimulated CD25+CD4+ T cells from naive SJL mice secreted IL‐10 and IL‐10 soluble receptor (sR) partially reversed the in vitro suppressive activity of CD25+CD4+ T cells. CD25+CD4+ T cells from IL‐10‐deficient mice were unable to suppress active EAE. These findings demonstrate that CD25+CD4+ T cells suppress pathogenic autoreactive T cells in actively induced EAE and suggest they may play an important natural regulatory function in controlling CNS autoimmune disease through a mechanism that involves IL‐10.