Human CD4+ T cells can be classified as either naïve, central memory (TCM), or effector memory (TEM) cells. To identify the CD4+ T cell subsets most important in the pathogenesis of rheumatoid arthritis (RA), we phenotypically defined human CD4+ T cells as functionally distinct subsets, and analyzed the distribution and characteristics of each subset in the peripheral blood. We classified CD4+ T cells into six novel subsets based on the expression of CD45RA, CCR7, CD27, and CD28. The CCR7 + CD45RA-CD27 + CD28+ TCM subset comprised a significantly smaller proportion of CD4+ T cells in RA patients compared to healthy controls. The frequency of TNF-α-producing cells in the CCR7-CD45RA-CD27 + CD28+ TEM subset was significantly increased in RA. Furthermore, within the CCR7 + CD45RA-CD27 + CD28+ TCM subset, which was decreased in periperal blood from RA, the proportions of total Foxp3+ Treg cells and CD45RA-Foxp3(high) activated/effector Treg cells were significantly lower in RA patients. Our findings suggest that the increased proportion of TNF-α-producing cells and the decreased proportion of CD45RA-Foxp3(high) activated/effector Treg cells in particular subsets may have critical roles in the pathogenesis of RA.
Keywords: Activated/effector Treg cells; CTLA4; Central memory T cells; DAS28m; DC; DMARD; ECD; Effector memory T cells; Foxp3; HCPB; Inflammatory cytokines; PB; PerCPCy5.5; RA; RAPB; Regulatory T cells; Rheumatoid arthritis; SLE; T(CM); T(EM); Treg; central memory T cells; cytotoxic T-lymphocyte antigen 4; dendritic cell; disease activity score for 28 joints; disease-modifying anti-rheumatic drug; effector memory T cells; energy-coupled dye; forkhead box P3; peridin chlorophyll protein-cyanin 5.5; peripheral blood; peripheral blood from RA patients; peripheral blood from healthy controls; regulatory T cells; rheumatoid arthritis; systemic lupus erythematosus.
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