Collagen II-primed Foxp3 Transduced T Cells Ameliorate Collagen-induced Arthritis in Rats: The Effect of Antigenic Priming on T Regulatory Cell Function
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.
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style='mso-spacerun:yes'> ADDIN EN.REFLIST
1. Tengvall S, Eneljung T, Jirholt P, Turesson O, Wing K, Holmdahl R, et al. Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis. PloS one 2016; 11(5):e0154630.
2. Wang F, Yu J, Wang Y, Jiang Y, Guo N, Zhang W. Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats. Appl Microbiol Biotechnol 2015; 99(15):6327-37.
3. Steiner G. Auto-antibodies and autoreactive T-cells in rheumatoid arthritis: pathogenetic players and diagnostic tools. Clin Rev Allergy Immunol 2007; 32(1):23-36.
4. Bugatti S, Vitolo B, Caporali R, Montecucco C, Manzo A. B cells in rheumatoid arthritis: from pathogenic players to disease biomarkers. BioMed Res Int 2014; 2014:681678.
5. Rezaiemanesh AR, Abdolmaleki M, Abdolmohammadi K, Aghaei H, DadgarPakdel F, Fatahi Y, et al. Immune cells involved in the pathogenesis of ankylosing spondylitis. Biomed. Pharmacother 2018:198-204.
6. Williams RO. Collagen-induced arthritis as a model for rheumatoid arthritis. Methods Mol Med 2004; 98:207-16.
7. Ria F, Penitente R, De Santis M, Nicolo C, Di Sante G, Orsini M, et al. Collagen-specific T-cell repertoire in blood and synovial fluid varies with disease activity in early rheumatoid arthritis. Arthritis Res Ther 2008; 10(6):R135.
8. Toh ML, Miossec P. The role of T cells in rheumatoid arthritis: new subsets and new targets. Curr Opin Rheumatol 2007; 19(3):284-8.
9. Daryabor G, Mahmoudi M, Jamshidi A, Nourijelyani K, Amirzargar A, Ahmadzadeh N, et al. Determination of IL-23 receptor gene polymorphism in Iranian patients with ankylosing spondylitis. Eur Cytokine Netw 2014; 25(1):24-9.
10. Gol-Ara M, Jadidi-Niaragh F, Sadria R, Azizi G, Mirshafiey A. The role of different subsets of regulatory T cells in immunopathogenesis of rheumatoid arthritis. Arthritis 2012; 2012:805875.
11. Yu Q, Xu M, Yu F, Jin Y. CD4(+) CD25(+) regulatory T cells as a therapeutic target in rheumatoid arthritis. Cent Eur J Immunol 2014; 39(1):100-3.
12. Lan Q, Fan H, Quesniaux V, Ryffel B, Liu Z, Zheng SG. Induced Foxp3(+) regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases J Mol Cell Biol 2012; 4(1):22-8.
13. Fantini MC, Dominitzki S, Rizzo A, Neurath MF, Becker C. In vitro generation of CD4+ CD25+ regulatory cells from murine naive T cells. Nat. Protoc 2007; 2(7):1789-94.
14. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003; 299(5609):1057-61.
15. Marta Kisgati Æ Reto Asmis. Generation of retroviruses for the overexpression of cytosolic and mitochondrial glutathione reductase in macrophages in vivo. Cytotechnology 2007; 54:5-14. Pmid:1900301314.
16 Morgan ME, Flierman R, van Duivenvoorde LM, Witteveen HJ, van Ewijk W, van Laar JM, et al. Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. Arthritis Rheum 2005; 52(7):2212-21.
17. Lee J, Lee J, Park MK, Lim MA, Park EM, Kim EK, et al. Interferon gamma suppresses collagen-induced arthritis by regulation of Th17 through the induction of indoleamine-2,3-deoxygenase. PloS one 2013; 8(4):e60900.
18. Haque R, Lei F, Xiong X, Wu Y, Song J. FoxP3 and Bcl-xL cooperatively promote regulatory T cell persistence and prevention of arthritis development. Arthritis Res Ther 2010; 12(2):R66.
19. Catchpole B, Staines NA, Hamblin AS. Antigen presentation of Type II collagen in rats. Clin Exp Immunol 2001; 125(3):478-84.
20. Andersen KG, Butcher T, Betz AG. Specific Immunosuppression with InducibleFoxp3-Transduced Polyclonal T cells. PLoS Biol 2008; 6(11):e276.
21. Baeke F, Korf H, Overbergh L, Verstuyf A, Thorrez L, Van Lommel L, et al. The vitamin D analog, TX527, promotes a human CD4+CD25highCD127low regulatory T cell profile and induces a migratory signature specific for homing to sites of inflammation. J Immunol 2011; 186(1):132-42.
22. Yao Y, Vent-Schmidt J, McGeough MD, Wong M, Hoffman HM, Steiner TS, et al. Tr1 Cells, but Not Foxp3+ Regulatory T Cells, Suppress NLRP3 Inflammasome Activation via an IL-10-Dependent Mechanism. J. Immunol 2015; 195(2):488-97.
23. Asnagli H, Martire D, Belmonte N, Quentin J, Bastian H, Boucard-Jourdin M, et al. Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis. Arthritis Res Ther 2014; 16(3):R115.
24. Chen SY, Wu CL, Lai MD, Lin CC, Yo YT, Jou IM, et al. Amelioration of rat collagen-induced arthritis through CD4+ T cells apoptosis and synovial interleukin-17 reduction by indoleamine 2,3-dioxygenase gene therapy. Hum Gene Ther 2011; 22(2):145-54.
25. Wang Q, Wang L, Wu L, Zhang M, Hu S, Wang R, et al. Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. Sci. Rep 2017; 7:45364.
26. Porporatto C, Canali MM, Bianco ID, Correa SG. The biocompatible polysaccharide chitosan enhances the oral tolerance to type II collagen. Clin Exp Immunol 2009; 155(1):79-87.
27. Wang X, Ma Y, Yoder A, Crandall H, Zachary JF, Fujinami RS, et al. T cell infiltration is associated with increased Lyme arthritis in TLR2-/- mice. F FEMS Immunol Med Microbiol 2008; 52(1):124-33.
28. Vremec D, Pooley J, Hochrein H, Wu L, Shortman K. CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen. J Immunol 2000; 164(6):2978-86.
29. Ellis SD, McGovern JL, van Maurik A, Howe D, Ehrenstein MR, Notley CA. Induced CD8+FoxP3+ Treg cells in rheumatoid arthritis are modulated by p38 phosphorylation and monocytes expressing membrane tumor necrosis factor alpha and CD86. Arthritis Rheum 2014; 66(10):2694-705.
30. Mottet C, Uhlig HH, Powrie F. Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells. J Immunol 2003; 170(8):3939-43.
31. Wing JB, Sakaguchi S. TCR diversity and Treg cells, sometimes more is more. Eur J Immunol 2011; 41(11):3097-100.
32. Pietrosimone KM, Jin M, Poston B, Liu P. Collagen-Induced Arthritis: A model for Murine Autoimmune Arthritis. Bio Protoc 2015; 5(20).
33. Song HP, Li X, Yu R, Zeng G, Yuan ZY, Wang W, et al. Phenotypic characterization of type II collagen-induced arthritis in Wistar rats. Exp Ther Med 2015; 10(4):1483-8.
34. L Dai, A Claxson, SL Marklund, R Feakins, N Yousaf, Y Chernajovsky and PG Winyard. Amelioration of antigen-induced arthritis in rats by transfer of extracellular superoxide dismutase and catalase genes. Gene Ther 2003; 10,550-8. PMID:12646860
35. Ganesan K, Selvam R, Abhirami R, Raju KV, Manohar BM, Puvanakrishnan R. Gender differences and protective effects of testosterone in collagen induced arthritis in rats. Rheumatol Int 2008; 28(4):345-53.
36. Charbonnier LM, Han WG, Quentin J, Huizinga TW, Zwerina J, Toes RE, et al. Adoptive transfer of IL-10-secreting CD4+CD49b+ regulatory T cells suppresses ongoing arthritis. J Autoimmun 2010; 34(4):390-9.
37. Zhang W, Wang F, Wang B, Zhang J, Yu JY. Intraarticular gene delivery of CTLA4-FasL suppresses experimental arthritis. Int Immunol 2012; 24(6):379-88.
38. Boissier MC, Feng XZ, Carlioz A, Roudier R, Fournier C. Experimental autoimmune arthritis in mice. I. Homologous type II collagen is responsible for self-perpetuating chronic polyarthritis. Ann Rheum Dis 1987; 46(9):691-700.
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