Faculty Publications and Presentations
Protection against Experimental Autoimmune Myocarditis Is Mediated by Interleukin-10-Producing T Cells that Are Controlled by Dendritic Cells
Biology | Chemistry
Experimental autoimmune myocarditis (EAM) can be induced in the Lewis rat by cardiac myosin or its cryptic S2-16 peptide epitope (amino acids1052 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- 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-. 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.
Li, Ya; Heuser, Janet S.; Kosanke, Stanley D.; Hemric, Mark E.; and Cunningham, Madeleine W., "Protection against Experimental Autoimmune Myocarditis Is Mediated by Interleukin-10-Producing T Cells that Are Controlled by Dendritic Cells" (2005). Faculty Publications and Presentations. 109.
Reproduced from Am J Pathol 2005, 167:1 5‐15with permission from the American Society for Investigative Pathology. For more information on the article, go to http://ajp.amjpathol.org/cgi/content/abstract/167/1/5?maxtoshow=&hits=10&RESULTFORMAT=&author1=hemric&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT .