Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein.
Following induction of experimental encephalomyelitis with a T-cell clone, L10C1, that is specific for the myelin basic protein epitope p87-99, the inflammatory infiltrate in the central nervous system contains a diverse collection of T cells with heterogeneous receptors. We show here that when clone L10C1 is tolerized in vivo with an analogue of p87-99, established paralysis is reversed, inflammatory infiltrates regress, and the heterogeneous T-cell infiltrate disappears from the brain, with only the T-cell clones that incited disease remaining in the original lesions. We found that antibody raised against interleukin-4 reversed the tolerance induced by the altered peptide ligand. Treatment with this altered peptide ligand selectively silences pathogenic T cells and actively signals for the efflux of other T cells recruited to the site of disease as a result of the production of interleukin-4 and the reduction of tumour-necrosis factor-alpha in the lesion.
Brocke
S
S
Department of Neurology and Neurological Sciences, Stanford University Medical Center, California 94305, USA.
Gijbels
K
K
Allegretta
M
M
Ferber
I
I
Piercy
C
C
Blankenstein
T
T
Martin
R
R
Utz
U
U
Karin
N
N
Mitchell
D
D
Veromaa
T
T
Waisman
A
A
Gaur
A
A
Conlon
P
P
Ling
N
N
Fairchild
P J
PJ
Wraith
D C
DC
O'Garra
A
A
Fathman
C G
CG
Steinman
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000276:immunology; D004679:Encephalomyelitis / Q000188:drug therapy* / Q000276:immunology; D000939:Epitopes; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology / Q000627:therapeutic use*; D010243:Paralysis / Q000276:immunology; D010446:Peptide Fragments / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D015847:Interleukin-4