Subpopulations of regulatory T cells in rheumatoid arthritis, systemic lupus erythematosus, and Behcet's disease

Abstract

Recently, subpopulations of regulatory T (Treg) cells, resting Treg (rTreg) and activated Treg (aTreg), have been discovered. The authors investigated the relationship between the change of Treg, aTreg and rTreg and autoimmune diseases. Treg cells and those subpopulations were analyzed by using the human regulatory T cell staining kit and CD45RA surface marker for 42 rheumatoid arthritis (RA), 13 systemic lupus sclerosis (SLE), 7 Behcet's disease (BD), and 22 healthy controls. The proportion of Treg cells was significantly lower in RA (3.8% ± 1.0%) (P < 0.001) and BD (3.3% ± 0.5%) (P < 0.01) compared to healthy controls (5.0% ± 1.3%). The proportion of aTreg cells was also significantly lower in RA (0.4% ± 0.2%) (P = 0.008) and BD (0.3% ± 0.1%) (P = 0.013) compared to healthy controls (0.6% ± 0.3%). The rTreg cells showed no significant differences. The ratio of aTreg to rTreg was lower in RA patients (0.4% ± 0.2%) than that in healthy controls (0.7% ± 0.4%) (P = 0.002). This study suggests that the decrement of aTreg not rTreg cells contributes the decrement of total Treg cells in peripheral blood of RA and BD autoimmune diseases. Detailed analysis of Treg subpopulations would be more informative than total Treg cells in investigating mechanism of autoimmune disease.

Keywords: Autoimmune Diseases; Behcet Disease; Regulatory T Cells; Rheumatoid Arthritis; Systemic Lupus Erythematosus.

Fig. 1

Detection of Treg cells and subpopulations by flowcytometry. (A) CD25 and FoxP3 expression in CD4⁺ cells. The gated (a) population was regarded as CD25^highFoxP3⁺ Treg cells. (B) CD25 and CD45RA expression in CD4⁺ cells. The gated (a) population was regarded as CD4⁺CD25⁺⁺⁺CD45RA^- activated Treg (aTreg) cells, the (b) population as CD4⁺CD25⁺⁺CD45RA⁺ resting Treg (rTreg) cells and (c) population was regarded as CD4⁺CD25⁺⁺CD45RA^- non-suppressive T cells. Treg, regulatory T cells; FoxP3, forkhead box P3; PE-Cy5, phycoerythrin-cyanin 5; PE, phycoerythrin.

Fig. 2

The proportion of CD3⁺CD4⁺ cells and the absolute CD4⁺ T cell count. (A) The proportion of CD4⁺ in CD3⁺ T cell was significantly lower in SLE group than RA, BD, or healthy controls. (B) The absolute count of the CD4⁺ T cells was significantly lower in SLE group than RA or healthy controls. RA, rheumatoid arthritis; BD, Behcet's disease; SLE, systemic lupus erythematosus; HC, healthy controls; Treg, regulatory T cells; aTreg, activated Treg cells; rTreg, resting Treg cells.

Fig. 3

Comparison of proportions of total Treg cells, aTreg and rTreg subpopulations. (A) The proportion of Treg cells was significantly lower in RA and BD than healthy controls. (B) The proportion of aTreg cells was significantly lower in RA and BD compared to healthy controls. (C) The proportions of rTreg were not different between disease groups and healthy controls. (D) RA patients showed a significantly decreased ratio of aTreg to rTreg. RA, rheumatoid arthritis; BD, Behcet's disease; SLE, systemic lupus erythematosus; HC, healthy controls; Treg, regulatory T cells; aTreg, activated Treg cells; rTreg, resting Treg cells.