International Immunology Advance Access published online on August 16, 2006
International Immunology, doi:10.1093/intimm/dxl080
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1 Neuroimmunology Laboratory, Department of Biochemistry, La Trobe University, Bundoora, Victoria 3086, Australia
* To whom correspondence should be addressed. 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
Received March 29, 2006
Accepted July 19, 2006
Article
A BAFF antagonist suppresses experimental autoimmune encephalomyelitis by targeting cell-mediated and humoral immune responses
Nicholas D. Huntington 1, Ryo Tomioka 2, Chelsea Clavarino 1, Anne M. Chow 1, David Liñares 1, Paula Maña 1, Jamie Rossjohn 3, Teresa G. Cachero 4, Fang Qian 4, Susan L. Kalled 5, Claude C. A. Bernard 1, and Hugh H. Reid 6 *
2 Neuroimmunology Laboratory, Department of Biochemistry, La Trobe University, Bundoora, Victoria 3086, Australia; Present address: Department of Neurology, Saitama Medical School, 38 Morohongo, Moroyama, Iruma-gun, Saitam 350-0495, Japan
3 Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Faculty of Medicine, Monash University, Clayton, Victoria 3168, Australia
4 Department of Protein Engineering, Cambridge, MA 02142, USA
5 Department of Molecular and Cell Biology, Biogen Idec Inc., Cambridge, MA 02142, USA
6 Neuroimmunology Laboratory, Department of Biochemistry, La Trobe University, Bundoora, Victoria 3086, Australia; Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Faculty of Medicine, Monash University, Clayton, Victoria 3168, Australia
Hugh H. Reid, E-mail: hugh.reid{at}med.monash.edu.au
Abstract 
, 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.
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