The proportion and phenotypic changes of CD4+CD25−Foxp3+ T cells in patients with untreated rheumatoid arthritis

Abstract

Objective CD4+CD25+Foxp3+ regulatory T (Treg) cell-mediated immunosuppression is an essential mechanism of rheumatoid arthritis (RA). However, little is known regarding the specific role of CD4+CD25−Foxp3+ Treg cells in RA. This study aimed to investigate the frequency of circulating CD4+CD25−Foxp3+ Treg cells and their role in RA. Methods Sixty-one untreated RA patients and 40 healthy controls (HCs) were enrolled in this study. The proportion of CD4+CD25−Foxp3+ T cells and CD4+CD25+Foxp3+ Tregs; the levels of CTLA4, GITR, Helios, and ICOS; and the production of IL-17A, IFN-γ, and IL-10 were assessed by flow cytometry. The correlation of CD4+CD25–Foxp3+ T cells and CD4+CD25+Foxp3+ Tregs with the clinical indicators was conducted by Spearman correlation analysis. Results The proportion of CD4+CD25–Foxp3+ T cells was elevated in RA and positively correlated with disease activity. CD4+CD25–Foxp3+ T cells expressed less Helios and produced more IFN-γ than conventional Tregs in RA. Additionally, the proportion of CD4+CD25–Foxp3+ T cells was positively correlated with DAS28 score, IgG titer, and anti-CCP titer. Conclusions These data indicate that CD4+CD25−Foxp3+ T cells in RA exhibit several different functional properties from conventional Tregs and are correlated with RA disease activity.

Increased circulating CD39+FoxP3+CD4+ regulatory T cells in Early Rheumatoid Arthritis facilitate the antiinflammatory action of methotrexate and associate with the clinical response

“…Despite intensive research there is still controversy regarding the frequency, phenotype and function of regulatory T (Treg) cells in established [7–9,31,32] or early RA [6,11,12,33,34]. Frequencies have been shown to be, when compared with HC, either increased [6,9,33,34], akin [31] or decreased [11,12].…”

“…Despite intensive research there is still controversy regarding the frequency, phenotype and function of regulatory T (Treg) cells in established [7–9,31,32] or early RA [6,11,12,33,34]. Frequencies have been shown to be, when compared with HC, either increased [6,9,33,34], akin [31] or decreased [11,12]. In addition, Treg cell function has been described as increased in patients with ERA [6] and in mice at the early phase of experimental RA [35] but also decreased [7,32] or similar [11,31] to HC in patients with early or longstanding RA.…”

“…In addition, Treg cell function has been described as increased in patients with ERA [6] and in mice at the early phase of experimental RA [35] but also decreased [7,32] or similar [11,31] to HC in patients with early or longstanding RA. Of note, Lawson et al [11] reported decreased proportions of circulating Tregs in ERA with preserved functional capacity; in contrast, Cribbs et al found that the function but not the number of Treg cells was altered in DMARD-naïve RA [7]; other investigators have reported decreased [12] or increased [33,34] numbers of circulating Tregs in ERA but did not study their suppressive capacity. In addition, Cribbs et al [7] described that treatment with DMARDs normalized the altered Treg cell function in previously untreated patients and at the same time induced an elevation of Treg cell numbers above those observed in HC [7]; however, Ehrenstein et al showed that whereas DMARDs were not able to restore the altered Treg cell function or to elevate Treg cell numbers in RA above HC levels, anti-TNF drugs did achieve both of these objectives [32].…”

Identification of unstable regulatory and autoreactive effector T cells that are expanded in patients with FOXP3 mutations

“…Collectively, these data contribute to the basic knowledge about the role of FOXP3 as a gatekeeper of T reg identity and quiescence as well as in preventing autoreactive T eff expansion in humans. In addition, these data are of interest from a translational perspective, such as in the context of T reg -based therapies, not only in patients with IPEX but also in patients with other autoimmune diseases in which the loss-of-identity T regs and expansion of autoreactive T cells are still poorly defined or where similar T reg instability has been suggested ( 46 , 47 ).…”

Identification of ANKRD13D as a potential target in renal cell carcinomas

“…PE-conjugated FOXP3, PC5.5-conjugated CD4 and PC7-conjugated CD25 were purchased from BD (Becton, Dickinson and Company, Franklin Lakes, NJ, USA). 22 Reverse transcription polymerase chain reaction (RT-qPCR) was performed by One-step SYBR® PrimeScript™ Kit II (TaKaRa Dalian Biotechnology Co., Ltd Dalian, China) on Bio-Rad iQ5 Real-Time PCR Detection System. The primers were acquired from primer bank (Primer Bank ID 269315851c3).…”