Current address: Dr. Fahad Haroon, Department of Clinical Research, Hamdard University, New Delhi, India.
Astrocytic Fas ligand expression is required to induce T-cell apoptosis and recovery from experimental autoimmune encephalomyelitis
Article first published online: 21 NOV 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
European Journal of Immunology
Volume 43, Issue 1, pages 115–124, January 2013
How to Cite
Wang, X., Haroon, F., Karray, S., Martina Deckert and Schlüter, D. (2013), Astrocytic Fas ligand expression is required to induce T-cell apoptosis and recovery from experimental autoimmune encephalomyelitis. Eur. J. Immunol., 43: 115–124. doi: 10.1002/eji.201242679
- Issue published online: 16 JAN 2013
- Article first published online: 21 NOV 2012
- Accepted manuscript online: 26 SEP 2012 03:32AM EST
- Manuscript Accepted: 19 SEP 2012
- Manuscript Revised: 24 AUG 2012
- Manuscript Received: 14 MAY 2012
In T-cell-mediated autoimmune diseases of the CNS, apoptosis of Fas+ T cells by FasL contributes to resolution of disease. However, the apoptosis-inducing cell population still remains to be identified. To address the role of astrocytic FasL in the regulation of T-cell apoptosis in experimental autoimmune encephalomyelitis, we immunized C57BL/6 glial fibrillary acid protein (GFAP)-Cre FasLfl/fl mice selectively lacking FasL in astrocytes with MOG35–55 peptide. GFAP-Cre FasLfl/fl mice were unable to resolve EAE and suffered from persisting demyelination and paralysis, while FasLfl/fl control mice recovered. In contrast to FasLfl/fl mice, GFAP-Cre FasLfl/fl mice failed to induce apoptosis of Fas+ activated CD4+ T cells and to increase numbers of Foxp3+ Treg cells beyond day 15 post immunization, the time point of maximal clinical disease in control mice. The persistence of activated and GM-CSF-producing CD4+ T cells in GFAP-Cre FasLfl/fl mice also resulted in an increased IL-17, IFN-γ, TNF, and GM-CSF mRNA expression in the CNS. In vitro, FasL+ but not FasL− astrocytes induced caspase-3 expression and apoptosis of activated T cells. In conclusion, FasL expression of astrocytes plays an important role in the control and elimination of autoimmune T cells from the CNS, thereby determining recovery from EAE.