Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 229, Issue 1-2, Pages 91-97Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2010.07.007
Keywords
Regulatory T cells; Fas/FasL; Perforin; EAE; TCR vaccination
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Funding
- National Institutes of Health [RO1AI052227]
- MSNRI
- DNRG
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Autoaggressive, myelin-reactive T cells are involved in multiple sclerosis and its prototype experimental autoimmune encephalomyelitis (EAE) in mice. A peripheral negative feedback mechanism involving regulatory CD4+ and CD8+T cells (Treg) operates to suppress disease-mediating T cell responses. We have recently characterized a novel population of Qa-1a-restricted, TCR-peptide-reactive CD8 alpha alpha+TCR alpha beta+ Treg that induce apoptotic depletion of the encephalitogenic V beta 8.2 cells in vivo and provide protection from EAE. Here we have used mice deficient in perforin. Fas/FasL and IFN-gamma molecules to investigate their role in Treg-mediated regulation of EAE. Data show that Fas/FasL interactions are not involved, but regulation mediated by Treg is dependent on the presence of IFN-gamma and the perforin pathway. These data provide a molecular mechanism of Treg-mediated killing of the pathogenic T cells and have important implications in the design of immune interventions for demyelinating disease. (C) 2010 Elsevier B.V. All rights reserved.
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