Measurement of natural (CD4+CD25high) and inducible (CD4+IL-10+) regulatory T cells in patients with systemic lupus erythematosus

Baráth, Sándor; Aleksza, Magdolna; Tarr, Tünde; Sipka, Sándor; Szegedi, Gyula; Kiss, Emese

doi:10.1177/0961203307080226

Cited by 67 publications

(47 citation statements)

References 31 publications

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“…These findings support the idea that alterations in the balance between inflammatory and regulatory mediators may help identify patients at risk of disease flare and help decipher SLE pathogenic mechanisms [84]. Concerning the role of regulatory T cells in SLE, most studies point to a reduction in Treg cell number and function in SLE [85][86][87]. The role of Th17 cells has been described in the pathogenesis of SLE and several studies have reported an increase in Th17 cells and IL17 in SLE, and in particular with disease flare [88][89][90].…”

Section: Cytokines and Immune-regulatory Defectssupporting

confidence: 72%

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Nakken

Bodolay

Szodoray

2014

Clinic Rev Allerg Immunol

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Undifferentiated connective tissue disease (UCTD) is a unique clinical entity, a potential forerunner of well-established systemic autoimmune/rheumatic diseases. UCTD is characterized by the presence of various clinical symptoms, as well as a diverse repertoire of autoantibodies, resembling systemic autoimmune diseases. Since approximately one-third of these patients consequently transform into a full-blown systemic autoimmune/rheumatic disease, it is of major importance to assess pathogenic factors leading to this progression. In view of the fact that the serological and clinical picture of UCTD and systemic autoimmune diseases are very similar, it is assumed that analogous pathogenic factors perpetuate both disease entities. In systemic autoimmune conditions a quantitative and qualitative impairment of regulatory T cells have been shown previously and in parallel a relative dominance of proinflammatory Th17 cells has been introduced. Moreover the imbalance between regulatory and Th17 cells plays a pivotal role in the initiation and propagation of UCTD. Additionally, we depict a cytokine imbalance, which give raise to a biased T-cell homeostasis from the UCTD phase throughout the fully developed systemic autoimmune disease stage. The levels of IL-6, IL-12, IL-17, IL-23 and IFN- were pathologically increased with a parallel reduction of IL-10. We believe that the assessment of Th17/Treg cell ratio, as well as the simultaneous quantitation of cytokines may give a useful diagnostic tool at the early UCTD stage to identify patients with a higher chance of consecutive disease progression towards serious systemic autoimmune diseases. Moreover, the early-targeted immunomodulating therapy in these patients may decelerate, or even stop this progression, before the development of serious autoimmune conditions with organ damage.

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Section: Cytokines and Immune-regulatory Defectssupporting

confidence: 72%

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Nakken

Bodolay

Szodoray

2014

Clinic Rev Allerg Immunol

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“…A defective suppressor ability was found in some studies reveal decreased numbers of circulating CD4?CD25? Tregs in SLE patients, in combination with inefficient clearance of apoptotic cells, may contribute to the onset of SLE [19][20][21][22][23], but other studies did not confirm such an alteration; some other studies had reported unaltered proportions or even increased proportions of Treg in patients with SLE [24][25][26][27]. Furthermore, Foxp3?CD4?…”

Section: Discussionmentioning

confidence: 92%

Elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in patients with lupus nephritis

et al. 2011

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To investigate the variations of T-helper 17 (Th17) and regulatory T (Treg) cells in patients with lupus nephritis (LN), a total of 60 systemic lupus erythematosus patients and 28 healthy controls (HCs) were enrolled. The frequency of Th17 cells and Treg cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometric analysis. The serum concentrations of interleukin-17 (IL-17) and transforming growth factor-beta 1 (TGF-β1) were measured by enzyme-linked immunosorbent assay (ELISA). The results demonstrated in LN patients a significant decrease in the frequency of CD4+CD25(high) and CD4+CD25+FoxP3+ T cells and a significant increase in the frequency of Th17 cells in peripheral blood, and the ratio of Th17 to Treg cell frequency was significantly increased along with increased SLEDAI scores. LN patients had a lower percentage and expression of FoxP3 in CD4+CD25(high) T cells than SLE patients without nephritis. The concentration of TGF-β1 was found decreased in SLE patients compared with that from healthy controls, though no significant difference was found between LN patients and SLE patients without nephritis. The expression of IL-17 levels in LN patients exhibited a significant increase compared with patients without nephritis and healthy controls. Based on our results, the significantly elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in lupus nephritis, suggesting that Th17/Treg functional imbalance may be involved in the pathogenesis of renal damage in SLE patients.

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“…These divergent results could arise due to diVerences in the populations of patients, the methods used to purify/detect Tregs, or how the suppression assays were performed. Most groups found a signiWcantly decreased percentage of regulatory T cells in the group of patients compared to healthy individuals [24][25][26][27][28][29] while some others described a signiWcant increase in this cell population in peripheral blood [30][31][32][33][34]. This inconsistency might show the existence of diVerent variable factors with diVerent impact on the expansion and survival of Tregs which demands more patients of diverse background to be examined.…”

Section: Discussionmentioning

confidence: 93%

Quantification of regulatory T cells in peripheral blood of patients with systemic lupus erythematosus

Habibagahi

Jaberipour

et al. 2010

Rheumatol Int

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Regulatory T cells (Tregs) are supposed to stop immune responses in the course of immune activation. However, chronic activation of immune system in systemic lupus erythematosus (SLE) and many other autoreactive disorders are evidence of malfunction of this system. Therefore, it is plausible to quantify presence of these cells in different diseases. Forty-one patients with diagnosis of SLE were enrolled in this study. Patients were divided into two groups of patients with active and inactive disease based on the disease activity score. Flow cytometry analysis was used to determine the frequency of regulatory T cells in peripheral blood according to high expression of CD25 and intracellular Forkhead/winged-helix (Foxp3). Further 30 healthy individuals considered as control group. Significantly less CD4+CD25hi regulatory T cells were detected in active patients (P < 0.001) compared to healthy individuals. The percentage of CD4+CD25hi cells were inversely correlated with the SLEDAI disease score in patients with active disease (r = -0.837, P < 0.0001). Patients with active disease had lower frequencies of CD4+Foxp3+ cells. However, increased frequencies of CD4+Foxp3+ T cells were observed in peripheral blood of patients with inactive disease compared with active patients or healthy individuals (P < 0.010). Moreover, a significant difference between the proportion of CD4+CD25-Foxp3+ population in healthy controls and patients with active disease was shown (P < 0.0005). Presence of lower frequencies of Tregs in patients with SLE could be evaluated as an immune turbulence and could be employed as a target for immunotherapeutic manipulation. However, controversies need to be resolved.

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Measurement of natural (CD4+CD25high) and inducible (CD4+IL-10+) regulatory T cells in patients with systemic lupus erythematosus

Cited by 67 publications

References 31 publications

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in patients with lupus nephritis

Quantification of regulatory T cells in peripheral blood of patients with systemic lupus erythematosus

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