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Experimental arthritis induced in mice by collagen type II associated with ovalbumin: modulation by oral tolerance


Rheumatoid arthritis (RA) is an autoimmune disease that affects human cartilage and synovial tissue, due to the activation of T and B lymphocytes reactive to type II collagen present in the joints. Although there is no experimental model that mimics all the features of human disease, the collagen-induced arthritis (CIA) in mice DBA/1 is the main model for study of this disease. Recently it was shown that the CIA could also be induced in mice with others MHC haplotypes, as the strain BALB/c, by administration of exogenous proteins associated with collagen, such as KLH (keyhole lympet hemocyanin) and OVA (ovalbumin ), emulsified in complete Freund's adjuvant (ACF). Manipulation of the immune system to the prophylaxis and treatment of autoimmunity has been studied in several laboratories. Promising results in preventing the installation of the CIA were obtained in experimental mice DBA/1, by oral administration of collagen before induction of disease. The oral tolerance is a special type of immune response of the digestive tract, leading to inhibition of systemic mechanisms of immunity that would normally be triggered by the administration of antigen by other means. The main cells involved in this process are the immature dendritic cells (iDCs) and regulatory T cells (Tregs), which activity culminated in anergy or clonal deletion of activated T cells. Because of its regulatory potential, oral tolerance may render therapies against various chronic inflammatory diseases, autoimmune in nature, making the understanding of its mechanisms an important goal to be reached. Thus, the purpose of this study is to assess whether tolerance induced by oral intake of OVA interferes with the induction and / or in the course of CIA caused by administration of OVA + CII in mice of strain BALB/c and investigate the effect of adoptive transfer of DCs isolated from mice tolerant to OVA on CIA. It is also purpose of this project to evaluate the in vitro interactions between DCs from tolerant mice and T lymphocytes of animals arthritis, with respect to lymphocyte proliferation, expansion of regulatory T cells and production of cytokines. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
THOME, RODOLFO; ROMANI FERNANDES, LUIS GUSTAVO; MINEIRO, MARCELA FRANCO; SIMIONI, PATRICIA UCELLI; JOAZEIRO, PAULO PINTO; DA SILVA CUNHA TAMASHIRO, WIRLA MARIA. Oral tolerance and OVA-induced tolerogenic dendritic cells reduce the severity of collagen/ovalbumin-induced arthritis in mice. Cellular Immunology, v. 280, n. 1, p. 113-123, NOV 2012. Web of Science Citations: 13.

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