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Effects of cystamine on antioxidant activities and regulatory T cells in lupus-prone mice.

ABSTRACT: Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells, are strongly associated with the pathogenesis of systemic lupus erythematosus (SLE). Despite the well-established beneficial effects of cystamine on lupus-prone mice, the extent to which cystamine contributes to antioxidant activity and the reduction of regulatory T cells has seldom been investigated. Therefore, this study elucidates how cystamine affects anti-oxidant activities in NZB/W F1 mice by performing assays of Glutathione (GSH), 1,1-diphenyl-2- picryl-hydrazyl (DPPH) and malondialdehyde thiobarbituric acid (MDA). In addition, investigations of the effects of cystamine on CD4(+) /CD25(+) regulatory T cells and interleukin-6 (IL6)/STAT-3 signalling were performed with flow cytometry and immunoblots. Experimental results reveal more significantly reduced MDA and increased GSH and DPPH in NZB/W F1 mice receiving cystamine than in those mice receiving PBS. Meanwhile, CD4(+) /CD25(+) regulatory T cells more significantly increase in NZB/W F1 mice receiving cystamine than in those mice receiving PBS, accompanied by significantly reduced IL-6/phosphorylated STAT-3 expression. The above findings suggest the beneficial effects of cystamine in terms of increasing antioxidant activities and CD4(+) /CD25(+) regulatory T cells in lupus-prone mice by suppressing IL-6/STAT3 signalling.

SUBMITTER: Hsu TC

PROVIDER: S-EPMC4159022 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Effects of cystamine on antioxidant activities and regulatory T cells in lupus-prone mice.

Hsu Tsai-Ching TC Chiu Chun-Ching CC Wang Yi-Wen YW Tzang Bor-Show BS

Journal of cellular and molecular medicine 20130802 10

Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells, are strongly associated with the pathogenesis of systemic lupus erythematosus (SLE). Despite the well-established beneficial effects of cystamine on lupus-prone mice, the extent to which cystamine contributes to antioxidant activity and the reduction of regulatory T cells has seldom been investigated. Therefore, this study elucidates how cystamine affects anti-oxidant activities in NZB/W F1 mice by ...[more]

PMID: 23905628

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Project description:Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown cause characterized by expansion of autoreactive lymphocytes. Regulatory T cells (T(regs)) are a component of the normal immune system and contribute to the maintenance of peripheral tolerance. T(reg) abnormalities have been associated with several autoimmune diseases and there is interest in the role of T(regs) in SLE. We previously demonstrated that transfer of expanded CD4(+)CD25(+)CD62L(HI) T(regs) slows the development of lupus in (NZBxNZW)F(1) (B/W) mice. However in the absence of T(reg) specific surface antigens, cell purification remains a compromise between the breadth and purity of the population isolated. Importantly, purified populations always contain Foxp3(-) effector T cells (T(effs)) that theoretically could exacerbate autoimmunity in the recipient. Here we explore the impact of transferring the more comprehensive, but less pure T(reg) subset defined by CD4(+)CD25(+) expression on development of murine lupus. All cells were FACS sorted and expanded prior to adoptive transfer. Development of proteinuria and survival were measured. We found that exogenous expansion of CD4(+)CD25(+) cells produced a population containing 70-85% CD4(+)Foxp3(+)T(regs). Expanded T(regs) had higher CTLA-4 and Foxp3 expression, increased in vitro suppression capacity, and prolonged in vivo survival as compared to freshly isolated cells. Adoptive transfer of expanded CD4(+)CD25(+) T(regs) inhibited the onset of glomerulonephritis and prolonged survival in mice. Importantly the population of T(eff) contained within the adoptively transferred cells had reduced survival and proliferation capacity as compared to either co-transferred T(regs) or transferred T(effs) expanded in the absence of T(regs). These studies demonstrate that adoptive transfer of expanded CD4(+)CD25(+)Foxp3(+)T(regs) has the capacity to inhibit the onset of murine lupus and that this capacity is significant despite transfer of co-cultured T(eff) cells. These data indicate that when co-expanded with regulatory T cells, exogenously activated T(effs) from autoimmune patients may not pose a significant risk of promoting disease.

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Effects of cystamine on antioxidant activities and regulatory T cells in lupus-prone mice.

Publications

Effects of cystamine on antioxidant activities and regulatory T cells in lupus-prone mice.

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