Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood

Lawson, Catherine A.; Brown, Andrew; Bejarano, Victoria; Douglas, Susan; Burgoyne, CH; Greenstein, Adam; Boylston, Arthur W.; Emery, Paul; Ponchel, Frédérique; Isaacs, John D.

doi:10.1093/rheumatology/kel089

Cited by 201 publications

(153 citation statements)

References 47 publications

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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: 85%

“…Similarly discrepant data were reported in RA patients; Lawson et al reported deficit in CD4+ CD25 bright regulatory cells in peripheral blood of early active RA compared to patients with reactive arthritis or control group [18]. However, Minami et al reported that the percentage of CD4+CD25+ T cells was higher in RA patients than controls, but it was not statistically significant [19].…”

Section: Introductionmentioning

confidence: 92%

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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: 85%

Section: Introductionmentioning

confidence: 92%

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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“…This evidence supports the idea that a deficiency of this cell subset may be a possible factor in susceptibility to RA [42]. This hypothesis seems to be further supported by investigations of the correlation between the percentage of Treg cells in PB and disease duration, which have confirmed higher numbers of circulating Treg cells in patients with long-standing disease [35,39].…”

Section: The Paradox Of Treg Cell Expansion In Ra Patientssupporting

confidence: 83%

Role of regulatory T cells in rheumatoid arthritis: facts and hypothesis

Alunno

Bartoloni

Nocentini

et al. 2010

Autoimmun Highlights

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Regulatory T cells (Treg) are a CD4 + lymphocyte subset involved in self-tolerance and autoimmunity prevention. There is evidence for a phenotypic and/or functional impairment of this cell subset during the natural history of several chronic autoimmune/inflammatory diseases, including rheumatoid arthritis (RA). Although the intracellular transcription factor FoxP3 is thought to be the master regulator of Treg cell function, a number of other molecules expressed on the cell surface have been proposed for the identification of Treg cells. This is important in order to favour their possible selective isolation and in the development of new therapeutic strategies. In the present paper, available data on phenotypic and functional characterization of Treg cells in both peripheral blood and synovial fluid from RA patients are reviewed and their possible pathogenic role in triggering and perpetuating rheumatoid joint inflammation is discussed.

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“…They also participate in the maintenance of immunological self-tolerance by suppressing immune responses mediated by autoreactive T cells that lead to autoimmune disease. In this context, Tregs are implicated in controlling several autoimmune diseases, such as type I diabetes (4), multiple sclerosis (5,6), and rheumatoid arthritis (7). Additionally, Tregs were reported to be defective in autoimmune polyglandular syndrome type II (8), autoimmune hepatitis (9), and in patients with primary biliary cirrhosis (10).…”

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confidence: 99%

Expansion of CD4+CD25+and FOXP3+ Regulatory T Cells during the Follicular Phase of the Menstrual Cycle: Implications for Human Reproduction

Arruvito¹,

Sanz²,

Banham

et al. 2007

The Journal of Immunology

387

325

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Regulatory T cells (Tregs) are thought to affect the severity of various infectious and autoimmune diseases. The incidence of autoimmune disease is higher in fertile women than in men. Thus, we investigated whether Treg numbers were modulated during the menstrual cycle by sex hormones. In fertile nonpregnant women, we detected an expansion of CD4+CD25+FOXP3+ Tregs in the late follicular phase of the menstrual cycle. This increase was tightly correlated with serum levels of estradiol and was followed by a dramatic decrease in Treg numbers at the luteal phase. Women who have had recurrent spontaneous abortions (RSA) showed similarly low numbers of Tregs at both the follicular and luteal phases, comparable to numbers we observed in postmenopausal women. In addition to decreased numbers, Tregs from women with RSA were also functionally deficient, as higher numbers were required to exert a similar magnitude of suppression to CD4+CD25+FOXP3+ cells from fertile women. Consequently, reproductive failure might result from the inability of Tregs in women with RSA to expand during the preimplantatory phase combined with their lower functional capacity. Additionally, the modulation of Treg numbers we observed in fertile women suggests that the stage of the menstrual cycle should be taken into account when Treg numbers are investigated clinically.

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Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood

Abstract: These data demonstrate a smaller CD4+CD25high regulatory T-cell population in peripheral blood of individuals with early active RA prior to disease-modifying treatment. This may be a contributory factor in the susceptibility to RA and suggests novel approaches to therapy.

Cited by 201 publications

References 47 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

Role of regulatory T cells in rheumatoid arthritis: facts and hypothesis

Expansion of CD4+CD25+and FOXP3+ Regulatory T Cells during the Follicular Phase of the Menstrual Cycle: Implications for Human Reproduction

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