Antigen-specific therapy promotes repair of myelin and axonal damage in established EAE.
Inflammation results in CNS damage in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. It is uncertain how much repair of injured myelin and axons can occur following highly selective anti-inflammatory therapy in EAE and MS. In this study, SJL/J mice with established EAE were treated successfully with an antigen-specific recombinant T cell receptor ligand (RTL), RTL401, a mouse I-A(s)/PLP-139-151 construct, after the peak of EAE. To define the mechanisms by which late application of RTL401 inhibits EAE, we evaluated mice at different time points to assess the levels of neuroinflammation and myelin and axon damage in their spinal cords. Our results showed that RTL401 administered after the peak of acute EAE induced a marked reduction in inflammation in the CNS, associated with a significant reduction of demyelination, axonal loss and ongoing damage. Electron microscopy showed that RTL-treated mice had reduced pathology compared with mice treated with vehicle and mice at the peak of disease, as demonstrated by a decrease in continued degeneration, increase in remyelinating axons and the presence of an increased number of small, presumably regenerative axonal sprouts. These findings indicate that RTL therapy targeting encephalitogenic T cells may promote CNS neuroregenerative processes.
Wang
Chunhe
C
Neuroimmunology Research, Veterans Affairs Medical Center, Portland, Oregon, USA. wangch@ohsu.edu
Gold
Bruce G
BG
Kaler
Laurie J
LJ
Yu
Xiaolin
X
Afentoulis
Michael E
ME
Burrows
Gregory G
GG
Vandenbark
Arthur A
AA
Bourdette
Dennis N
DN
Offner
Halina
H
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D004334:Drug Administration Schedule; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D000939:Epitopes; D005260:Female; D007167:Immunotherapy; D008024:Ligands; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013116:Spinal Cord / Q000648:ultrastructure*
D000939:Epitopes; D008024:Ligands; C514432:RTL401 fusion protein; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins