CD45RA−Foxp3low non-regulatory T cells in the CCR7−CD45RA−CD27+CD28+ effector memory subset are increased in synovial fluid from patients with rheumatoid arthritis

• The CD27+CD28+ TEM subset is increased in the CD4+ T cells in synovial fluids from RA (RASF).
• Increase in Foxp3+CD4+ cells in RASF is due to increased number of CD45RA−Foxp3low non-Treg cells.
• CD45RA−Foxp3low non-Treg cells in the CD27+CD28+ TEM subset are increased in RASF.

Increased numbers of regulatory T (Treg) cells are found in synovial fluid from patients with rheumatoid arthritis (RASF) compared with peripheral blood. However, Treg cells in RASF have been shown to have a decreased capacity to suppress T cells. Here we phenotypically classified CD4+ T cells in RASF into six subsets based on the expression of CD45RA, CCR7, CD27 and CD28, and demonstrated that the CCR7−CD45RA−CD27+CD28+ TEM subset was significantly increased in synovial fluid compared with peripheral blood. In addition, the proportion of Foxp3+ Treg cells in the CCR7−CD45RA−CD27+CD28+ TEM subset was significantly increased in RASF. Furthermore, most of the Foxp3+ Treg cells in RASF were non-suppressive CD45RA−Foxp3low non-Treg cells, and the frequency of the non-Treg cells in the CCR7−CD45RA−CD27+CD28+ TEM subset was significantly increased in RASF. Our findings suggest that the pro-inflammatory environment in RA joints may induce the increase of CD45RA−Foxp3low non-Treg cells in synovial fluid.