Enrichment of CD4+ CD25high T cell population in patients with systemic lupus erythematosus treated with glucocorticoids

López, Patricia; Gómez, Jesús María Fernández; Gutiérrez, Carmen

doi:10.1136/ard.2005.049924

Cited by 137 publications

(92 citation statements)

References 30 publications

(22 reference statements)

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“…The mean (± SD) percentages of CD4+CD25 bright as well as the total CD4+ CD25+ T cells are in line with the published "normal" values [9,16,17]. CD4+CD25+ T cells have been investigated in several autoimmune diseases, presenting conflicting results in most cases [14][15][16][17][18][19][20][21][22]. These discrepancies may be attributed to the differences in the selection of patients (active or inactive diseases) or probably due to technical difficulties in CD4+ CD25+ T cells phenotypic characterization.…”

Section: Fig (2) Percentages Of Cd4+ Cd25supporting

confidence: 53%

“…A recent study done by Azab et al showed that the levels of CD4+CD25+ % T cells in SLE patients were higher than in the control group, but it was statistically insignificant [14]. Also Suárez et al [15] found no significant difference of CD4+CD25+ % T cells between SLE patients and control group. On the other hand, several studies reported a decrease in the percentage of CD4+CD25+ T cells in SLE patients [16,17].…”

Section: Introductionmentioning

confidence: 94%

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Quantification of CD4' CD25' Regulatory T Cells in Peripheral Blood of Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis

Al-Shukaili¹,

Alkaabi²,

Al-Gafri³

et al. 2009

TOAUTOJ

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Recent animal studies have shown that regulatory T cells play a crucial role in the suppression of the immune response and that depletion of this subset of T cells might lead to development of autoimmune diseases. The aim of this work was to quantify regulatory T cells (CD4+ CD25+) in the peripheral blood of Omani patients with Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA) and correlate these findings with the disease activity of the patients. Thirty patients with SLE, 30 patients with RA and 25 healthy volunteers were enrolled in this study. Patients were divided into highly active or low active groups, depending on the disease activity. Flow cytometer was used to quantify CD4+ CD25+ T cells in the peripheral blood mononuclear cells (PBMC). We found that both highly active SLE (0.242 ± 0.3) and RA (0.56 ± 0.29) patients had significantly (p<0.001) lower levels of CD4+CD25 bright T cells than did normal controls (1.74 ± 0.47%) or patients with low disease activity (SLE=1.54 ± 0.33, RA=1.829 ± 0.76). The decreased number of CD4+CD25 bright T cells during disease activity was restored in remitting phase of SLE patients. This data provides further evidence supporting the hypothesis of defect of regulatory T cells in SLE and RA patients; which may have an important implication in the context of the control of the inflammation and development of autoimmunity.

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Section: Fig (2) Percentages Of Cd4+ Cd25supporting

confidence: 53%

Section: Introductionmentioning

confidence: 94%

Quantification of CD4' CD25' Regulatory T Cells in Peripheral Blood of Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis

Al-Shukaili¹,

Alkaabi²,

Al-Gafri³

et al. 2009

TOAUTOJ

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“…Using CD25 as the identifying marker, initial studies showed that decreased numbers of CD4ϩ,CD25ϩ Treg cells might contribute to the pathogenesis of SLE in humans (9,10). However, recent studies have demonstrated that the numbers of Treg cell subsets, including typical CD4ϩ,CD25 high or CD4ϩ,FoxP3ϩ Treg cells, were not decreased in SLE patients as compared with normal controls (11,12). So far, there have been conflicting reports regarding Treg cell function in lupus patients.…”

mentioning

confidence: 97%

Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon‐α–producing antigen‐presenting cells

Yan¹,

Ye²,

Chen³

et al. 2008

Arthritis & Rheumatism

165

129

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Objective. To explore whether there are extrinsic factors that impair the suppressive function of CD4؉,CD25؉ regulatory T cells in patients with untreated active systemic lupus erythematosus (SLE).Methods. We studied 15 patients with untreated active SLE, 10 patients with SLE in remission, and 15 healthy control subjects. Percentages of CD4؉,CD25؉, FoxP3؉ Treg cells and levels of forkhead box P3 (FoxP3) protein were analyzed by flow cytometry. Expression of messenger RNA (mRNA) for FoxP3 in purified Treg cell populations was assessed by real-time polymerase chain reaction analysis. Experiments examining Treg cell function in SLE were designed to distinguish primary from secondary T cell dysfunction. Levels of interferon-␣ (IFN␣) in supernatants from the function assays were determined with an IFN-stimulated response element-luciferase reporter assay.Results. The percentage of CD4؉,CD25؉, FoxP3؉ cells in peripheral blood was significantly increased in SLE patients as compared with controls (mean ؎ SEM 9.11 ؎ 0.73% versus 4.78 ؎ 0.43%; P < 0.0001). We found no difference in FoxP3 expression at either the mRNA or protein level in any CD4؉,CD25؉ T cell subset from SLE patients as compared with controls. Antigen-presenting cells (APCs) from SLE patients were responsible for decreased Treg cell activity and could also render dysfunctional Treg cells from healthy control subjects. CD4؉,CD25؉ Treg cells from SLE patients exhibited normal suppressive activity when cultured with APCs from healthy controls. A partial Treg cell blockade effect was induced by the high levels of IFN␣ derived from SLE patient APCs.Conclusion. We suggest that blockade of Treg cell-mediated suppression by IFN␣-producing APCs in SLE patients may contribute to a pathogenic loss of peripheral tolerance in this disease.

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“…Corticosteroid treatment of SLE was associated with increased numbers of Treg [230], while CD25-blocking antibody Daclizumab resulted in decreased Treg numbers in multiple sclerosis that was not related to clinical outcome [231]. In contrast, treatment of rheumatoid arthritis with Infliximab, which blocks the TNF receptor, induced increased frequencies of Treg that did correlate with improved clinical outcome [232].…”

Section: Treg Immunotherapymentioning

confidence: 98%

Regin in Blood Immune Regulation in Type 1 Diabetes

Pihl¹

2013

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Type 1 Diabetes (T1D) is an autoimmune disease resulting in insulin deficiency as a result of autoimmune destruction of pancreatic β-cells. Preserving β-cell function in patients with T1D would be of great benefit since patients with sustained endogenous insulin secretion are known to suffer less from secondary complications due to hyperglycemia. Glutamic acid decarboxylase 65 (GAD 65 ) is a major autoantigen targeted by self-reactive lymphocytes in T1D, and has been used in several attempts at treating T1D by inducing tolerance to β-cell antigens. We showed positive clinical effects of GAD 65 formulated with aluminium hydroxide (GAD-alum) on preservation of C-peptide secretion in a phase II clinical trial. Unfortunately, a phase III clinical trial in a larger population failed to confirm this finding. Regulatory T cells (Treg) are instrumental in maintaining peripheral tolerance to self-antigens. Deficiencies in Treg function are thought to influence the pathogenesis of autoimmune diseases, including T1D. One proposed mechanism of achieving tolerance to β-cell antigens in T1D is the induction of antigen-specific Treg through immunomodulation. The general aim of this thesis was to study immune regulation in T1D, the role of Treg and immunomodulatory effects of GAD-alum treatment in particular. Our hypothesis was that Treg biology is altered in T1D and pre-diabetes, and that an induction of GAD 65 -specific Treg contributes to the clinical efficacy of GAD-alum treatment. We demonstrated that T cells expressing Treg-associated markers were increased in number in patients with recent-onset T1D, as well as in children with high risk of developing T1D. We found that antigen recall 4 years after GAD-alum treatment induced cells with both regulatory and effector phenotypes in GAD-alum treated patients. Furthermore there was no effect on Treg-mediated suppression in GAD-alum treated patients, while patients with T1D, regardless of treatment, exhibited deficient Treg-mediated suppression of Teff that was intrinsic to the Treg population. We followed patients participating in a phase III trial of GAD-alum, and using an extended antibody panel we risk, but found no effects of variant alleles on the risk of developing T1D, or on the efficacy of GAD-alum treatment. We show small effects on C-peptide secretion and autoantibody positivity in patients with T1D. In conclusion, we find that while Treg are deficient in patients with T1D, induction of Treg is an unlikely mechanism of action of GAD-alum treatment. SUPERVISOR

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Enrichment of CD4+ CD25high T cell population in patients with systemic lupus erythematosus treated with glucocorticoids

Cited by 137 publications

References 30 publications

Quantification of CD4' CD25' Regulatory T Cells in Peripheral Blood of Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis

Quantification of CD4' CD25' Regulatory T Cells in Peripheral Blood of Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis

Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon‐α–producing antigen‐presenting cells

Regin in Blood Immune Regulation in Type 1 Diabetes

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