Intrathecal Fas ligand infusion strengthens immunoprivilege of central nervous system and suppresses experimental autoimmune encephalomyelitis.
Fas ligand (FasL) is an essential molecule strongly expressed in some immunoprivileged sites, but is expressed at very low levels in normal CNS. In this study, acute experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats with guinea pig myelin basic protein. Intrathecal infusion of recombinant FasL before EAE onset dose dependently suppressed acute EAE and alleviated pathological inflammation in lumbosacral spinal cord. This treatment greatly increased apoptosis in CNS inflammatory cells, but did not inhibit systemic immune response to myelin basic protein. Systemic administration of a similar dose of rFasL was ineffective. In vitro, encephalitogenic T cells were highly sensitive to rFasL-induced cell death, and activated macrophages were also susceptible. In addition, in vitro rFasL treatment potentiated the immunosuppressive property of rat cerebrospinal fluid. We conclude that intrathecal infusion of rFasL eliminated the initial wave of infiltrating T cells and macrophages, and therefore blocked the later recruitment of inflammatory cells into CNS. Although Fas receptor expression was observed on spinal cord neurons, astrocytes, and oligodendrocytes, no damage to these cells or to the myelin structure was detected after rFasL infusion.
Zhu
Bing
B
Brain Research Center, Vancouver Hospital and Health Sciences Center, University of British Columbia, Vancouver, Canada. bingzhu@interchange.ubc.ca
Luo
Liqing
L
Chen
Yongliang
Y
Paty
Donald W
DW
Cynader
Max S
MS
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D053222:Fas Ligand Protein; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007278:Injections, Spinal; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009186:Myelin Sheath / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D013116:Spinal Cord / Q000473:pathology
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins