Blockade of OX40-ligand after initial triggering of the T helper 2 response inhibits mercuric chloride-induced autoimmunity.
Mercuric chloride (HgCl2)-induced autoimmunity in Brown Norway rats is a spontaneously resolving autoimmune response driven by the activation of T helper type 2 lymphocytes (Th2 cells). Treatment with antibody to OX40-ligand (OX40-L) from the time of the first HgCl2 injection for 12 days had little effect. Delayed treatment commenced 8 days after the first HgCl2 injection significantly suppressed immunoglobulin E production, splenomegaly, weight loss and mortality. This makes OX40/OX40-L signalling an attractive therapeutic target for Th2-driven autoimmune diseases. Intravenous administration of the murine antibody to OX-40-L elicited a vigorous anti-mouse immunoglobulin antibody response that was significantly enhanced compared to the response to control immunoglobulin. It is likely that this response significantly reduced the plasma half-life of the anti-OX40-L antibody and this observation has clear implications for the interpretation of data from experiments where anti-OX40-L is used in vivo.
Department of Cellular and Molecular Medicine: Renal Medicine, St. George's, University of London, London, UK. imacphee@sgul.ac.uk
Iain A M
IA
MacPhee
Hideo
H
Yagita
David B G
DB
Oliveira
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D015551:Autoimmunity / Q000187:drug effects; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007073:Immunoglobulin E / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D008627:Mercuric Chloride / Q000276:immunology; D009929:Organ Size; D051381:Rats; D011914:Rats, Inbred BN; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000473:pathology; D016019:Survival Analysis; D018418:Th2 Cells / Q000276:immunology*; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D008562:Membrane Glycoproteins; C504587:Tnfsf4 protein, rat; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; D007073:Immunoglobulin E; D008627:Mercuric Chloride