Dual role for Fas ligand in the initiation of and recovery from experimental allergic encephalomyelitis.
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.
Sabelko-Downes
K A
KA
Departments of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri 63110, USA.
Cross
A H
AH
Russell
J H
JH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology*; D053222:Fas Ligand Protein; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell