Collagen II-primed Foxp3 Transduced T Cells Ameliorate Collagen-induced Arthritis in Rats: The Effect of Antigenic Priming on T Regulatory Cell Function

Abstract

Regulatory T cells (Tregs) play a major role in the prevention of autoimmune diseases. Transfer of Foxp3 gene into conventional T cells converts their phenotype to regulatory T cells. Therefore, the question arises as to whether adoptively transferred in vitro differentiated Treg cells specific for a locally expressed antigen might have better inhibitory effects on the progression of the disease as compared with antigen-nonspecific T reg cells.
 Herein, we investigated the therapeutic potential of primed and unprimed retrovirus mediated Foxp3-overexpression T cells following intravenously injected of these cells into affected rats with collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis.
 Our analyses demonstrate that systemic administration of collagen II primed Foxp3-transduced T cells could markedly ameliorate CIA inflammatory responses at clinical (p<0.0014) and pathological exchanges including cellular infiltration (p=0.002), bone erosion (p=0.0013) and synovial hyperplasia (p=0.002). In contrast, collagen II unprimed Foxp3-transduced T cells like as collagen II primed or unprimed GFP-transduced T cells did not reveal any beneficial effects on arthritis features as compared with untreated group (p>0.05).
 Therefore, we believe that collagen II primed Foxp3-transduced T cells are interacting locally and systemically with immune cells which reveled with decreasing of T cells infiltration into joints along with specific CII IgG production. Considering the results described here, it appears that the using patients' T cells which previously exposed to specific antigens may have more effective therapeutic advantage in the production of induced regulatory T cells in the treatment of arthritis.

Chemical composition and anti-arthritic activity of the essential oil from <i>Litsea cubeba</i> against Type II collagen rheumatoid arthritis in rat collagen

“…Its induced immune response, pathological features, and inflammatory manifestations are similar to those observed in human RA. Thus, it is widely used to study disease pathogenesis, screen potential therapeutic drugs, and study the effects of anti-RA drugs [19,20].…”

Function and Role of Regulatory T Cells in Rheumatoid Arthritis

“…CD4 + CD127 low/-CD25 + T cells, particularly the expansion of CD45RA + subsets, produces a high yield of Treg cells that maintain high Foxp3 expression in the absence of rapamycin (128,129). In the presence of anti-CD3/anti-CD28 and IL-2, this scheme can increase the number of cells up to thousands of times without losing the inhibitory activity of Treg cells (130). Since IL-2 is a key cytokine required for T cell activation and proliferation and nTregs express CD25 at high levels, they are highly sensitive to IL-2 stimulation.…”

Cell‐based therapies for the treatment of rheumatoid arthritis

“…Expansion of CD4 + CD127low/−CD25 + T cells, especially the CD45RA+ subset, generates high yields of Treg cells that maintain high expression of Foxp3 expression even in the absence of rapamycin 138,139 . In the presence of anti‐CD3/anti‐CD28 and IL‐2, the number of cells elevates thousands‐folds with no loss of their inhibitory effect on Treg cells 140 . IL‐2 is a key cytokine required for T cell activation and proliferation, and nTregs express high levels of CD25, receptors for IL‐2, making them highly sensitive to IL‐2 stimulation.…”