Involvement of IFN-gamma and perforin, but not Fas/FasL interactions in regulatory T cell-mediated suppression of experimental autoimmune encephalomyelitis.

Authors: Beeston, T  Smith, TR  Maricic, I  Tang, X  Kumar, V 
Citation: Beeston T, etal., J Neuroimmunol. 2010 Dec 15;229(1-2):91-7. Epub 2010 Aug 12.
Pubmed: (View Article at PubMed) PMID:20708278
DOI: Full-text: DOI:10.1016/j.jneuroim.2010.07.007

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 CD8alphaalpha+TCRalphabeta+ Treg that induce apoptotic depletion of the encephalitogenic Vbeta8.2 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.


Disease Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 6482806
Created: 2012-05-03
Species: All species
Last Modified: 2012-05-03
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.