Blockade of OX40‐ligand after initial triggering of the T helper 2 response inhibits mercuric chloride‐induced autoimmunity

Summary 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...

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Bibliographic Details
Published in:Immunology 2006-03, Vol.117 (3), p.402-408
Main Authors: MacPhee, Iain A. M., Yagita, Hideo, Oliveira, David B. G.
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - therapeutic use
Autoimmune Diseases - chemically induced
Autoimmune Diseases - immunology
Autoimmune Diseases - prevention & control
autoimmunity
Autoimmunity - drug effects
B7-1 Antigen - immunology
B7-2 Antigen - immunology
costimulation
Enzyme-Linked Immunosorbent Assay - methods
Immunoglobulin E - biosynthesis
Male
Membrane Glycoproteins - antagonists & inhibitors
Membrane Glycoproteins - immunology
mercuric chloride
Mercuric Chloride - immunology
Organ Size
Original
OX40‐ligand
Rats
Rats, Inbred BN
Signal Transduction - immunology
Spleen - pathology
Survival Analysis
Th2
Th2 Cells - immunology
Tumor Necrosis Factors - antagonists & inhibitors
Tumor Necrosis Factors - immunology
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Summary:Summary 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.
ISSN:0019-2805
1365-2567
DOI:10.1111/j.1365-2567.2005.02314.x