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Putative immunomodulatory properties of dendritic cells in experimental arthritis induced by the association of Type II collagen and ovalbumin

Grant number: 09/06157-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2009
Effective date (End): July 31, 2010
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Wirla Maria da Silva Cunha Tamashiro
Grantee:Marcela Franco Mineiro
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Intestinal mucosa is a portal of entry for most pathogens that invade the body. The immune response generated in these tissues may present different characteristics, ranging from the elimination of pathogens to the local or systemic tolerance to dietary antigens. The tolerogenic response that follows the intake of proteins is characterized by low levels or absence of either specific antibodies and T lymphocytes. The oral tolerance is an immunological active process, mediated by multiple mechanisms similar to those observed in other peripheral regions, i.e., anergy, deletion and expansion of regulatory T cells. The antigen-presenting cells, particularly dendritic (DC), are also involved in oral tolerance. In this regard, data from literature indicate that immature DCs (iDCs) are able to induce regulatory T cells. The cytokine IL-10, secreted by iDCs, appears to act in order to convert immature DCs into tolerogenic presenting cells, and thereby contributes to the induction of tolerance. Rheumatoid arthritis (RA) is an inflammatory disease that affects cartilage and synovial tissue, due to the activation of T and B lymphocytes reactive to type II collagen present in the joints. The strain DBA/1 is the most extensively experimental model used in scientific research of RA. The inoculation of CII in this strain of mice led to the development of experimental arthritis named collagen-induced arthritis (CIA). Promising results in preventing the establishment of CIA in mice DBA/1 were obtained by oral administration of collagen, before the induction of disease. Recently it was shown that the CIA could also be induced in BALB/c - a non susceptible lineage - by the administration of collagen plus ovalbumin (OVA). Work in progress in our laboratory assessing the effect of oral tolerance to OVA on the course of CIA in BALB/c mice. In this project, we intend to evaluate the interactions between dendritic cells from BALB/c tolerant to OVA and T lymphocytes obtained from arthritic BALB/c mice regarding the proliferative activity and production of cytokines.