Recombinant TCR ligand reverses clinical signs and CNS damage of EAE induced by recombinant human MOG.
Increasing evidence suggests that in addition to T cell-dependent effector mechanisms, autoantibodies are also involved in the pathogenesis of MS, including demyelinating antibodies specific for myelin oligodendrocyte glycoprotein (MOG). Our previous studies have demonstrated that recombinant T cell receptor ligands (RTLs) are very effective for treating T cell-mediated experimental autoimmune encephalomyelitis (EAE). In order to expand the scope of RTL therapy in MS patients, it was of interest to study RTL treatment of EAE involving a demyelinating antibody component. Therefore, we evaluated the therapeutic effects of RTL551, specific for T cells reactive to mouse (m)MOG-35-55 peptide, on EAE induced with recombinant human (rh)MOG in C57BL/6 mice. We report that RTL551 therapy can reverse disease progression and reduce demyelination and axonal damage induced by rhMOG without suppressing the anti-MOG antibody response. This result suggests that T cell-mediated inflammation and associated blood-brain barrier dysfunction are the central contributors to EAE pathogenesis and that successful regulation of these key players restricts potential damage by demyelinating antibodies. The results of our study lend support for the use of RTL therapy for treatment of MS subjects whose disease includes inflammatory T cells as well as those with an additional antibody component.
Sinha
Sushmita
S
Neuroimmunology Research, Portland VA Medical Center, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA.
Subramanian
Sandhya
S
Emerson-Webber
Ashley
A
Lindner
Maren
M
Burrows
Gregory G
GG
Grafe
Marjorie
M
Linington
Christopher
C
Vandenbark
Arthur A
AA
Bernard
Claude C A
CC
Offner
Halina
H
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002490:Central Nervous System / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000473:pathology; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000627:therapeutic use*; D063308:Myelin-Oligodendrocyte Glycoprotein; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*
D016207:Cytokines; D008024:Ligands; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; C542327:RTL551 protein; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins