Quantification and phenotype of regulatory T cells in rheumatoid arthritis according to Disease Activity Score-28

Abstract

Here we studied and characterized different peripheral blood (PB) regulatory T cell (Treg) subsets in rheumatoid arthritis (RA) patients and tested the hypothesis that changes in these cells can be linked to the degree of inflammation and relapsing/remission periods. PB cells were examined from RA subjects (n = 60) with different disease activity score-28 (DAS28) and from healthy controls (n = 40). Frequencies of Treg subsets expressing characteristic membrane antigens, FoxP3 or intracellular cytokines were quantified by flow cytometry. We observed a decrease in the percentages of CD4(+)CD25(high), CD4(+)CD25(int), CD4(+)CD25(int/high)FoxP3(+), CD4(+)CD38(+), CD4(+)CD62L(+), CD8(+)CD25(high)CD45RA(+) and CD8(+)CD25(int)CD45RA(+) T cells in PB of RA patients compared to healthy controls. In addition, we found increased percentages of cells expressing membrane/intracellular regulatory antigens such as OX40 (CD134), CD45RB(low) or CTLA-4 (CD152), and a higher proportion of other T cell subsets including CD4(+)CTLA-4(+), CD4(+)IL10(+), CD4(+)CD25(int)IL10(+), CD4(+)CD25(int) TGFbeta(+), CD4(+)CD25(low) TGFbeta(+) and CD8(+)CD28(- ). We show that most of these changes parallel the intensity of inflammation, with lowest or highest values in patients with moderately/very active disease compared to healthy controls and at times to patients with inactive RA. The balance between these cell subsets and their antigen expression would determine the inflammation levels and could thus be linked to the relapsing/remission periods of the disease.

Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind placebo-controlled study

“…We did not find a significant imbalance in Tregs, on this regard, previous studies have found conflicting results as some papers described a decrease in Tregs [6–8], whereas others did not observe this decrease [9,10] or found an increase [11]. This discrepancy largely depends on differences in the study design [5].…”

“…Different studies on Treg phenotype and function in RA patients have obtained conflicting results [6–11], these cells may have a role in the control of bone erosions in RA as, in experimental models, are able to inhibit OCs formation and activity [12–13]. …”

Anti-Arthritic Activity of Schistosoma mansoni and Trichinella spiralis Derived-Antigens in Adjuvant Arthritis in Rats: Role of FOXP3+ Treg Cells

“…Though not fully elucidated, changes in these cells can be linked to the degree of inflammation and thus remission and relapse in RA. Supporting this concept, a decrease in the percentage of peripheral blood Foxp3 + Treg cells was reported in RA patients, and this decrease correlated with the severity of the disease [55]. Counterintuitively, an increase in the number of Treg cells was detected in joints and peripheral blood of RA patients in another study.…”

THE RELATIONSHIP OF FoxP3+ T REGULATORY CELLS TO DISEASE ACTIVITY AND ANTIBODY LEVELS IN EARLY RHEUMATOID ARTHRITIS

“…В литературе представлены противоречивые данные о взаимосвязи количества Т рег с активностью заболевания и уровнями острофазовых показателей. Так, в ряде работ выявлена обратная корреляционная взаимосвязь между DAS28 и ПК циркулирующих Foxp3+ Т рег [16,21,22]. С другой стороны, среди пациентов с высокой активно-стью заболевания авторы регистрируют высокое содержа-ние CD25+Foxp3+ Т-клеток [21,25].…”

“…В настоящее время в литературе представлено боль-шое количество работ, посвященных оценке уровня и фе-нотипа Т рег при РА как в периферическом кровотоке, так и в синовиальной жидкости [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26], однако полученные в них данные весьма противоречивы и требуют дальнейше-го уточнения. Полагают, что количественный дефект CD4+CD25+Foxp3+CD127-регуляторных клеток особен-но характерен для раннего РА и ассоциируется с риском развития РА у бессимптомных пациентов, позитивных по антителам к циклическому цитруллинированному пептиду (АЦЦП) [27,28].…”