NDLI: The complement inhibitor FUT-175 suppresses T cell autoreactivity in experimental autoimmune encephalomyelitis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Li, Qing Nacion, Kristine Bu, Hong Lin, Feng
Description	Country affiliation: United States Author Affiliation: Li Q ( Assistant Professor, Institute of Pathology, Case Western Reserve University School of Medicine, 2085 Adelbert Road, Room 306, Cleveland, OH 44106, USA.)
Abstract	Several recent studies have shown that interacting antigen presenting cells and/or T cells produced complement activation products C5a and C3a, are integrally involved in T-cell activation, and promote the generation of myelin oligodendrocyte glycoprotein (MOG(35-55))-specific interferon-gamma and interleukin-17-producing T cells in experimental autoimmune encephalomyelitis, a rodent model of multiple sclerosis. In this study, we tested whether FUT-175, a clinical pharmaceutical that has been shown to inhibit the formation of C3/C5 convertases, can attenuate myelin-specific T-cell responses, as well as disease severity in experimental autoimmune encephalomyelitis. In vitro, FUT-175 inhibited local C5a/C3a production by antigen presenting cell-T-cell complexes and attenuated MOG(35-55)-specific Th1 and Th17 responses with little nonspecific cytotoxicity. In vivo administration of FUT-175 delayed experimental autoimmune encephalomyelitis disease onset, lowered clinical scores, decreased central nervous system inflammation, and reduced demyelination. The FUT-175-treated mice exhibited decreased numbers of MOG(35-55)-specific interferon-gamma- and interleukin-17-producing T cells. In addition, results from the FUT-175 treatment of naive recipients of adoptively transferred splenocytes from MOG(35-55)-immunized mice suggested that the effect of FUT-175 was on MOG-specific cellular responses and not on anti-MOG antibodies. These results argue that complement regulators, which inhibit C5a/C3a production, may have therapeutic efficacy in multiple sclerosis and in other clinical conditions in which T cells drive disease pathogenesis.
File Format	HTM / HTML
ISSN	00029440
e-ISSN	15252191
DOI	10.2353/ajpath.2009.081093
Journal	The American Journal of Pathology
Issue Number	2
Volume Number	175
Language	English
Publisher	Elsevier (on behalf of the American Society for Investigative Pathology)
Publisher Date	2009-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Mice, Inbred C57bl Drug Therapy Serine Proteinase Inhibitors Discipline Pathology Guanidines Administration & Dosage Pharmacology Biosynthesis Drug Effects Complement C3-c5 Convertases Antagonists & Inhibitors Encephalomyelitis, Autoimmune, Experimental T-lymphocytes Immunology Animals Mice
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

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The Complement Inhibitor FUT-175 Suppresses T Cell Autoreactivity in Experimental Autoimmune Encephalomyelitis

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The Complement Inhibitor FUT-175 Suppresses T Cell Autoreactivity in Experimental Autoimmune Encephalomyelitis

Mycobacterium bovis bacille Calmette-Guérin infection in the CNS suppresses experimental autoimmune encephalomyelitis and Th17 responses in an IFN-gamma-independent manner.

The complement system contributes to the pathology of experimental autoimmune encephalomyelitis by triggering demyelination and modifying the antigen-specific T and B cell response.

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