The influence of therapy on CD4+CD25<sup>high</sup>FOXP3+ regulatory T cells in systemic lupus erythematosus patients: a prospective study

Tselios, Konstantinos; Sarantopoulos, Alexandros; Gkougkourelas, Ioannis; Boura, Panagiota

doi:10.3109/03009742.2014.922214

Cited by 22 publications

(12 citation statements)

References 30 publications

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“…The present study supports the results of prior studies regarding improvement in the levels of circulating Treg cells following disease remission . This improvement in Treg frequency was seen as early as 3 months in the responder group, even though it showed a mild non‐significant decline after 3 months.…”

Section: Discussionsupporting

confidence: 91%

Effect of induction therapy on circulating T‐helper 17 and T‐regulatory cells in active proliferative lupus nephritis

et al. 2018

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Section: Discussionsupporting

confidence: 91%

Effect of induction therapy on circulating T‐helper 17 and T‐regulatory cells in active proliferative lupus nephritis

et al. 2018

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“…Most current treatments are unsuccessful in stopping disease reoccurrence after remission and may have unacceptable side effects after long-term use [11]. Although the mechanism is not understood, Tregs have been seen to modestly increase with the use of drugs not targeting Tregs, such as pyridostigmine, rituximab, azathioprine, and IVIG [190–193]. Corticosteroids lack specificity and importantly cause severe adverse effects such as bruising, abnormal weight gain, behavior changes, oral thrush, and others [194].…”

Section: Main Textmentioning

confidence: 99%

Regulatory T cells in multiple sclerosis and myasthenia gravis

Danikowski

Jayaraman

Prabhakar

2017

J Neuroinflammation

256

197

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Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs). Tregs are thought to play a critical role in the maintenance of peripheral immune tolerance. It is believed that Tregs function by suppressing the effector CD4+ T cell subsets that mediate autoimmune responses. Dysregulation of suppressive and migratory markers on Tregs have been linked to the pathogenesis of both MS and MG. For example, genetic abnormalities have been found in Treg suppressive markers CTLA-4 and CD25, while others have shown a decreased expression of FoxP3 and IL-10. Furthermore, elevated levels of pro-inflammatory cytokines such as IL-6, IL-17, and IFN-γ secreted by T effectors have been noted in MS and MG patients. This review provides several strategies of treatment which have been shown to be effective or are proposed as potential therapies to restore the function of various Treg subsets including Tr1, iTr35, nTregs, and iTregs. Strategies focusing on enhancing the Treg function find importance in cytokines TGF-β, IDO, interleukins 10, 27, and 35, and ligands Jagged-1 and OX40L. Likewise, strategies which affect Treg migration involve chemokines CCL17 and CXCL11. In pre-clinical animal models of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune myasthenia gravis (EAMG), several strategies have been shown to ameliorate the disease and thus appear promising for treating patients with MS or MG.

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“…These results are in line with numerous published reports showing an imbalance between Treg cells and effector T cells in active SLE [ 11 , 12 ]. Numerous studies have also shown that the number of Treg cells returns to normal values when the disease is inactive [ 5 , 10 , 13 ]. Therefore, the manipulation of Treg cells to increase their number is considered an interesting potential therapeutic strategy to develop in SLE.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have suggested that the induction of Treg cells may contribute to the immunosuppressive effects of glucocorticoids [ 24 – 28 ]. In SLE, a slight increase in the proportion of circulating Treg cells has been reported in patients taking oral prednisone [ 29 – 31 ]; the time to Treg cell recovery was reduced in patients treated with IV high dose MP [ 13 ]. However, to our knowledge, there has been no detailed report on the short-term effects of IV high dose MP on the different subsets of FoxP3 + T cells in active SLE until now.…”

Section: Introductionmentioning

confidence: 99%

Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus

et al. 2015

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Background/PurposeA slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE.MethodsWe prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA− cells; and (3) non-suppressive FoxP3lowCD45RA− cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score.ResultsSeventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53–8.43) at day 0 to 2.80% (0.83–14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50–12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02–20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20–17.70) at day 0 to 4.74% (1.03–9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2.ConclusionIV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE.

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The influence of therapy on CD4+CD25^highFOXP3+ regulatory T cells in systemic lupus erythematosus patients: a prospective study

Abstract: Increase in Tregs during SLE remission is independent of the therapeutic regimen used and probably represents an epiphenomenon of disease remission. Time to Tregs restoration was significantly shorter in patients treated with iv MP and IVIGs compared to CYP pulse therapy.

Cited by 22 publications

References 30 publications

Effect of induction therapy on circulating T‐helper 17 and T‐regulatory cells in active proliferative lupus nephritis

Effect of induction therapy on circulating T‐helper 17 and T‐regulatory cells in active proliferative lupus nephritis

Regulatory T cells in multiple sclerosis and myasthenia gravis

Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus

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The influence of therapy on CD4+CD25highFOXP3+ regulatory T cells in systemic lupus erythematosus patients: a prospective study

Abstract: Increase in Tregs during SLE remission is independent of the therapeutic regimen used and probably represents an epiphenomenon of disease remission. Time to Tregs restoration was significantly shorter in patients treated with iv MP and IVIGs compared to CYP pulse therapy.

Cited by 22 publications

References 30 publications

Effect of induction therapy on circulating T‐helper 17 and T‐regulatory cells in active proliferative lupus nephritis

Effect of induction therapy on circulating T‐helper 17 and T‐regulatory cells in active proliferative lupus nephritis

Regulatory T cells in multiple sclerosis and myasthenia gravis

Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus

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The influence of therapy on CD4+CD25^highFOXP3+ regulatory T cells in systemic lupus erythematosus patients: a prospective study