Anti-aquaporin-4 antibody induces astrocytic cytotoxicity in the absence of CNS antigen-specific T cells.
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Anti-aquaporin-4 antibody (AQP4-Ab) is a highly specific serum autoantibody that is detected in patients with NMO. Several lines of evidence indicate that AQP4-Ab not only serves as a disease marker but also plays a pivotal role in the pathogenesis of NMO. Although the pathogenicity of AQP4-Ab in vivo has recently been demonstrated, the presence of CNS antigen-specific T cells is recognized as a prerequisite for the antibody to exert pathogenic effects. Thus, it remains unclear whether AQP4-Ab is the primary cause of the disease or a disease-modifying factor in NMO. Here we report that pre-treatment with complete Freund's adjuvant (CFA) alone is sufficient for AQP4-Ab to induce astrocytic damage in vivo. Our results show the primary pathogenic role of AQP4-Ab in the absence of CNS antigen-specific T cells, and suggest that danger signals provided by nonspecific inflammation can be a trigger for those who harbor the autoantibody to develop NMO.
Kinoshita
Makoto
M
Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nakatsuji
Yuji
Y
Kimura
Takashi
T
Moriya
Masayuki
M
Takata
Kazushiro
K
Okuno
Tatsusada
T
Kumanogoh
Atsushi
A
Kajiyama
Koji
K
Yoshikawa
Hiroo
H
Sakoda
Saburo
S
D000818:Animals; D051401:Aquaporin 4 / Q000276:immunology*; D001253:Astrocytes / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005620:Freund's Adjuvant / Q000493:pharmacokinetics; D006801:Humans; D009471:Neuromyelitis Optica / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D005620:Freund's Adjuvant