Open AccessComplement regulatory protein Crry/p65 costimulation expands natural Treg cells with enhanced suppressive properties in proteoglycan‐induced arthritis
Author(s) -
Ojeda Gloria,
Pini Eliana,
Eguiluz César,
MontesCasado María,
Broere Femke,
van Eden Willem,
Rojo Jose M.,
Portolés Pilar
Publication year - 2011
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.30328
Subject(s) - foxp3 , immunology , il 2 receptor , biology , immune system , antigen , microbiology and biotechnology , population , t cell , medicine , environmental health
Abstract Objective To investigate the costimulatory role of Crry/p65 (Crry), a membrane complement regulatory protein, on the expansion and function of natural Treg cells and their ability to ameliorate proteoglycan‐induced arthritis (PGIA), an animal model of inflammatory arthritis in which the role of natural Treg cells is not well established. Methods CD4+CD25+ natural Treg cells from BALB/c mice were activated in vitro and costimulated by Crry. The expanded cells were phenotypically characterized, and their suppressive effect on T cell proliferation was assayed in vitro. The potential prophylactic and therapeutic effects of this population versus those of natural Treg cells in PGIA were studied. The clinical score, histology, the antigen‐specific isotype antibody pattern, in vitro T cell responses, and the presence of Treg cells in the paws were studied. Results Crry costimulation enhanced the in vitro expansion of natural Treg cells while maintaining their phenotypic and suppressive properties. Crry‐expanded Treg cells had stronger suppressive properties in vivo and a longer ameliorating effect in the PGIA model than did natural Treg cells. Crry‐expanded Treg cells suppressed T cell– and B cell–dependent responses in PGIA, changing the pathogenic antibody isotype pattern and decreasing antigen‐dependent secretion of cytokines, including interferon‐γ, interleukin‐12 (IL‐12), and IL‐17. Increased FoxP3 expression was detected in the paws of mice transferred with Crry‐expanded Treg cells. Conclusion Crry‐mediated costimulation facilitates in vitro expansion of natural Treg cells while maintaining their suppressive properties in vitro and in vivo in the PGIA model. These results highlight the potential of the complement regulatory protein Crry to costimulate and expand natural Treg cells capable of suppressing disease in an animal model of chronic inflammatory arthritis.