Desensitization with Self-Antigen dsDNA Inhibits B and T-cell Functions by Modulating Treg as Regulator Immune System in Pristane-induced Lupus Mice Model

saiful arifin

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The aim of this study was to develop a novel therapeutic method for improving immune system regulation in SLE using escalating dose self-antigen dsDNA immunotherapy. Methods: Female Balb/c mice were given a single intraperitoneal injection of  0.5 ml pristane.. Starting at 12 weeks after injection,. the mice were evaluated for clinical and serological manifestations. Mice with lupus signs (PIL mice) were divided into four groups; positive control group, PIL A (0.01 μg/ml, 0.1 μg/ml, 1 μg/ml ) EDI dsDNA, PIL B (0.1 μg/ml, 1 μg/ml, 10 μg/ml ) EDI dsDNA, and PIL C(1 μg/ml, 10 μg/ml, 100 μg/ml). EDI dsDNA were administered once every week in consecutively. The doses would increase every week. dsDNA were complexed with the cationic polyethylenimine (PEI) before injection. Samples  were analyzed for autoantibodies levels (dsDNA, ANA) and ,TGF-β cytokine  from serum using ELISA and T-Reg, mature dendritic cells  from spleen using flowcytometry.. Results: Escalating dose antigen spesific immunotherapy with self-antigen dsDNA significantly decreased ANA (p=0.02), anti-dsDNA (p=0.03), dendritic cell mature  (p=0.02) compare to positive control, and not significantly decreases Th17 cells (p=0,18) but the result tend to get lower. Desensitization using self-antigen dsDNA was increased T-reg proliferation (p=0.00) and level of TGF-β (p=0.03) significantly compare to positive control. Conclusion: Desensitization using self-antigen dsDNA coupled to PEI was able to modulate T-Reg as a regulator immune respon and inhibit B and T cell functions in lupus mice model.


Systemic Lupus Erythematosus, dsDNA, escalating dose, tolerance, Treg

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Afzali B, Lombardi G, Lechler R I and Lord G M 2007 The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease Clin Exp.Immunol. 148 32-46

Elias K M, Laurence A, Davidson T S, Stephens G, Kanno Y, Shevach E M and Shea J J O 2008 Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3 / Stat-5 independent signaling pathway Blood 111 1013–20

Handono K, Marisa D and Kalim H 2016 Association between the low levels of vitamin D and Treg function in systemic lupus erythematosus patients Acta Med. Indones. 45 26–31

Kalim H 1996 Clinical features and life expectancy of systemic lupus erythematosus (SLE) Indonesian Journal of Medicine 46 383–4

Kessenbrock K, Krumbholz M, Schönermarck U, Back W, Gross W L, Werb Z, Gröne H J, Brinkmann V and Jenne D E 2009 Netting neutrophils in autoimmune small-vessel vasculitis. Nat. Med. 15 623–5

Pathak S and Mohan C 2011 Cellular and molecular pathogenesis of systemic lupus erythematosus: lessons from animal models Arthritis Res. Ther. 13 241

Rifa'i M, Kawamoto Y, Nakashima I and Suzuki H. Essential roles of CD8+ CD122+ regulatory T cells in the maintenance of T cell homeostasis J Exp. Med. 2004 200 1123-34.

Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T,Toda M and Takahashi T 2001 Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: Their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance Immunol. Rev. 18 18-32

Uyttenhove C and Van Snick J 2006 Development of an anti-IL-17A auto-vaccine that prevents experimental auto-immune encephalomyelitis Eur. J. Immunol. 36 2868–74

Xu D, Liu H, Komai-Koma M, Campbell C, McSharry C, Alexander J and Liew F Y 2003 CD4+CD25+ regulatory T cells suppress differentiation and functions of Th1 and Th2 cells, Leishmania major infection, and colitis in mice J. Immunol. 170 394–9


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