Chronic Active Arthritis Driven by Macrophages Without Involvement of T Cells: A Novel Experimental Model of Rheumatoid Arthritis.

OBJECTIVE: To develop a new chronic RA model which is driven by the innate immune system.METHOD: The injection of a cocktail of four monoclonal antibodies against collagen type II followed by intra-peritoneal injections of mannan (from Saccharomyces cerevisiae) on days 5 and 60 led to the development of chronic arthritis in B10.Q mice. The role of the innate versus the adaptive immune system in this arthritis model was investigated using genetically modified mouse strains.RESULT: A new model of chronic relapsing arthritis was characterized and found to lead to a persistent, chronic arthritis. This relapsing disease was driven by macrophages lacking the ability to make a reactive oxygen species (ROS) response and was associated with the classical/alternative, but not the lectin complement pathway. The disease was also independent of FcγRIII as well as adaptive immune cells, B and T cells, indicating the innate immune system, involving complement activation, as the sole driver of chronicity.CONCLUSION: Chronic active arthritis can be driven by macrophages without the involvement of T and B cells in the adaptive immune system. This article is protected by copyright. All rights reserved. (Less)