Protection against experimental autoimmune myocarditis is mediated by interleukin-10-producing T cells that are controlled by dendritic cells.

Abstract

Experimental autoimmune myocarditis (EAM) can be induced in the Lewis rat by cardiac myosin or its cryptic S2-16 peptide epitope (amino acids 1052 to 1076). To investigate cellular mechanisms and the role of antigen-presenting cells in regulation of myocarditis, we induced protection against EAM in Lewis rats by administration of S2-16 peptide in incomplete Freund's adjuvant (IFA). Protection to EAM was associated with activation of S2-16-reactive splenocytes secreting high levels of interleukin (IL)-10 and reduced levels of interferon-gamma and IL-2. Adoptive transfer of S2-16:IFA-induced splenocytes producing IL-10 suppressed myocarditis induction in syngeneic recipients, suggesting their regulatory cell nature. However, exposure of S2-16:IFA-induced cells to inflammatory cytokine IL-12 converted them to Th1 effectors that transferred EAM. Differentiated function of S2-16-reactive T cells in protected rats resulted from increased IL-10 production by dendritic cells (DCs). Purified DCs from S2-16:IFA-treated rats promoted S2-16-reactive CD4+ T cells to produce increased IL-10 and reduced interferon-gamma. In addition, adoptive transfer of IL-10-producing DCs from S2-16:IFA-treated rats also induced protection to EAM in recipient rats. These studies demonstrated DCs and key cytokines, such as IL-10 and IL-12, regulated the fate of T cells in myocarditis development in the Lewis rat.

• Authors: Ya Li, Janet S Heuser, Stanley D Kosanke, Mark Hemric, Madeleine W Cunningham
• Journal: The American journal of pathology (Am J Pathol) Vol. 167 Issue 1 Pg. 5-15 (Jul 2005) ISSN: 0002-9440 [Print] United States
• PMID: 15972947 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interleukin-10
• Interleukin-12
• Interferon-gamma
• Cardiac Myosins

Topics

• Adoptive Transfer
• Animals
• Antigen-Presenting Cells (immunology)
• Autoimmune Diseases (immunology, prevention & control)
• Cardiac Myosins (immunology)
• Cell Proliferation
• Dendritic Cells (immunology)
• Female
• Flow Cytometry
• Immunomagnetic Separation
• Interferon-gamma (biosynthesis, immunology)
• Interleukin-10 (biosynthesis, immunology)
• Interleukin-12 (biosynthesis, immunology)
• Myocarditis (immunology, prevention & control)
• Rats
• Rats, Inbred Lew
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes (immunology)