Autoimmune tolerance eliminates relapses but fails to halt progression in a model of multiple sclerosis.
To date there has been poor translation of immunotherapies from rodent models to treatment of progressive multiple sclerosis (MS). In the robust, relapsing Biozzi ABH mouse model of MS, using a combination of a transient deletion of T cells followed by intravenous (i.v.) myelin antigen administration, established relapsing disease in EAE can be effectively silenced. However, when treatment was initiated in late stage chronic-relapsing disease, despite inhibition of further relapses, mice demonstrated evidence of disease progression shown by a deterioration in mobility and development of spasticity and indicates that targeting relapsing, immunological components of MS alone is unlikely to be sufficient to control progression in the late stages of MS.
Pryce
Gareth
G
Department of Neuroinflammation, Institute of Neurology, University College London, 1 Wakefield Street, London WC1N 1PJ, UK.
O'Neill
Janet K
JK
Croxford
J Ludovic
JL
Amor
Sandra
S
Hankey
Deborah J
DJ
East
Emma
E
Giovannoni
Gavin
G
Baker
David
D
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015704:CD4 Antigens / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D007108:Immune Tolerance / Q000276:immunology*; D007275:Injections, Intravenous; D008212:Lymphocyte Depletion; D051379:Mice; D038602:Mice, Biozzi; D016513:Mice, SCID; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000517:prevention & control; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage / Q000276:immunology; D055502:Secondary Prevention; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D018991:Myelin Proteolipid Protein