International Immunology Advance Access originally published online on August 16, 2006
International Immunology 2006 18(10):1473-1485; doi:10.1093/intimm/dxl080
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A BAFF antagonist suppresses experimental autoimmune encephalomyelitis by targeting cell-mediated and humoral immune responses
1 Neuroimmunology Laboratory, Department of Biochemistry, La Trobe University, Bundoora, Victoria 3086, Australia
2 Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Faculty of Medicine, Monash University, Clayton, Victoria 3168, Australia
3 Department of Protein Engineering, Cambridge, MA 02142, USA
4 Department of Molecular and Cell Biology, Biogen Idec Inc., Cambridge, MA 02142, USA
5 Present address: Department of Neurology, Saitama Medical School, 38 Morohongo, Moroyama, Iruma-gun, Saitam 350-0495, Japan
Correspondence to: H. Reid; E-mail: hugh.reid{at}med.monash.edu.au
BAFF [B cell-activating factor of the tumour necrosis factor (TNF) family] and APRIL (a proliferation-inducing ligand) are two TNF family members with shared receptors. While, physiological roles for APRIL are not fully understood, BAFF is critical for B cell homeostasis and also acts as a co-stimulator of T cells. Using a B and T cell-mediated mouse model of multiple sclerosis (MS), myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), we observed that a BAFF/APRIL antagonist (soluble BCMA-Fc) inhibited central nervous system inflammation and demyelination such that it suppressed the onset and progression of clinical symptoms of EAE. In addition to dramatically reducing the titre of MOG-specific auto-antibodies, this treatment also induced a switch in the subtype of the Th cell population characterized by marked alterations in cytokine production following re-stimulation with MOG in vitro. Indeed, hBCMA-Fc therapy led to significant increases in the level of transforming growth factor ß, while the levels of Th1 cytokines were markedly diminished. These results not only identify BAFF as a critical factor in maintaining humoral immunity in EAE but also support its role in T lymphocyte responses. Our findings demonstrate that hBCMA-Fc acts on both effector arms of the immune response in EAE, a characteristic that may be of significant therapeutic value in the treatment of MS.
Keywords: autoimmunity, central nervous system diseases, cytokine receptors, cytokines, multiple sclerosis, therapeutics
Transmitting editor: D. Tarlinton
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Q. Lai Kwan Lam, O. King Hung Ko, B.-J. Zheng, and L. Lu Local BAFF gene silencing suppresses Th17-cell generation and ameliorates autoimmune arthritis PNAS, September 30, 2008; 105(39): 14993 - 14998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Dalakas Invited Article: Inhibition of B cell functions: Implications for neurology Neurology, June 3, 2008; 70(23): 2252 - 2260. [Abstract] [Full Text] [PDF]
|
|