title: Regulatory T cells play a role in T-cell receptor CDR2 peptide regulation of experimental autoimmune encephalomyelitis.
abstract: Eliciting T-cell receptor (TCR) -specific responsiveness has been known to provide an effective autoregulatory mechanism for limiting inflammation mediated by T effector cells. Our previous use of TCR peptides derived from the CDR3 regions of a pathogenic TCR effectively reversed ongoing experimental autoimmune encephalomyelitis (EAE) in a humanized TCR transgenic model. In this study, we use the TCR BV8S2 CDR2 peptide in the non-transgenic C57BL/6 EAE model to down-regulate the heterogeneous TCR BV8S2(+)  MOG-35-55-specific pathogenic T-cell population and demonstrate successful treatment of EAE after disease onset. Suppression of disease was associated with reduced MOG-35-55-specific and non-specific T-cell production of interleukin-17a and interferon-γ in the central nervous system, as well as reduced numbers of CD4(+)  and Foxp3(+)  T cells in the central nervous system. With the use of Foxp3-GFP and Foxp3 conditional knockout mice, we demonstrate that the TCR CDR2 peptide treatment effect is dependent on the presence of Foxp3(+)  regulatory T cells and that regulatory T cell numbers are significantly expanded in the periphery of treated mice. Hence, TCR CDR2 peptide therapy is effective in regulating heterogeneous, pathogenic T-cell populations through the activity of the Foxp3(+)  regulatory T cell population.
authors: Neuroimmunology Research, Department of Veterans Affairs Medical Center, Portland, OR 97239, USA. buenafea@ohsu.edu
authors: Abigail C
authors: AC
authors: Buenafe
authors: Shayne
authors: S
authors: Andrew
authors: Halina
authors: H
authors: Offner
authors: Arthur A
authors: AA
authors: Vandenbark
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta