The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/4/1195/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 8, April 19, 1999 1195-1205


Articles

Dual Role for Fas Ligand in the Initiation of and Recovery from Experimental Allergic Encephalomyelitis

Kimberly A. Sabelko-Downes*, Anne H. Cross{ddagger}, and John H. Russell*

From the * Departments of Molecular Biology and Pharmacology and the {ddagger} Department of Neurology, Washington University Medical School, St. Louis, Missouri 63110

We have previously demonstrated a role for Fas and Fas ligand (FasL) in the pathogenesis of experimental allergic encephalomyelitis (EAE). However, using an active induction paradigm we could not distinguish between FasL expressed on activated CD4+ T cells from that expressed on other inflammatory or resident central nervous system (CNS) cells. To address this issue, we have conducted reciprocal adoptive transfer experiments of nontransgenic or myelin basic protein–specific T cell receptor transgenic wild-type, lpr, or gld lymphocytes into congenic wild-type, lpr, and gld hosts. We found that FasL expressed on donor cells is important for the development of EAE, as FasL-deficient lymphocytes transfer attenuated disease. Furthermore, Fas expressed in the recipient animals is important for the progression of EAE, as clinical signs of disease in lpr recipients were dramatically attenuated after transfer of either wild-type or lpr T cells. Surprisingly, these experiments also identified CNS cells as a source of functional FasL. Host-derived FasL appears to be especially important in the recovery from EAE, as many gld recipients of wild-type lymphocytes develop prolonged clinical signs of disease. Thus it appears that FasL plays distinct roles in EAE during the initiation of and recovery from disease.

Key Words: autoimmunity • inflammation • T cell regulation • demyelinating disease • apoptosis


Address correspondence to John H. Russell, Department of Molecular Biology and Pharmacology, 660 S. Euclid Ave., St. Louis, MO, 63110 USA. Phone: 314-362-2558; Fax: 314-362-7058; E-mail: jrussell{at}pharmsun.wustl.edu.us

Abbreviations used: B6, C57BL/6; CNS, central nervous system; EAE, experimental allergic encephalomyelitis; FasL, Fas ligand; GVHD, graft-versus-host disease; MBP, myelin basic protein; MS, multiple sclerosis; TUNEL, TdT-mediated dUTP nick-end labeling.


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