Vaccination with amyloid-beta peptide induces autoimmune encephalomyelitis in C57/BL6 mice.
Recent experimental evidence shows that vaccination with amyloid-beta peptide (Abeta) of transgenic mouse models of Alzheimer's disease protects from the pathological accumulation of amyloid within the CNS. Phase I/II clinical trials of Abeta vaccination in mild to moderate Alzheimer's disease have been undertaken. Un expectedly, one of these trials has been suspended because 15 patients showed clinical signs consistent with CNS inflammation. Here, we show that C57BL/6 mice immunized with Abeta1-42 peptide develop an inflammatory disease of the CNS characterized by the presence both in the brain and spinal cord of perivenular inflammatory foci containing macrophages, T and B cells, and immunoglobulins. The experimental disease was observed only when pertussis toxin, an agent known to favour autoimmune processes, was co-administered. The immune-mediated CNS reaction was associated to Abeta-induced CD4(+) cells showing a Th1-type cytokine expression profile and to elevated levels of circulating anti-Abeta immunoglobulins. Our results indicate that vaccination with Abeta could determine, under certain circumstances, an aberrant autoimmune-type reaction to Abeta resulting in a perivenular inflammatory encephalomyelitis.
Furlan
Roberto
R
Neuroimmunology Unit, San Raffaele Scientific Institute, Milan, Italy.
Brambilla
Elena
E
Sanvito
Francesca
F
Roccatagliata
Luca
L
Olivieri
Stefano
S
Bergami
Alessandra
A
Pluchino
Stefano
S
Uccelli
Antonio
A
Comi
Giancarlo
G
Martino
Gianvito
G
D000544:Alzheimer Disease / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D037342:Pertussis Toxin / Q000276:immunology; D014611:Vaccination
D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D016207:Cytokines; D037342:Pertussis Toxin