title: CD45RA-Foxp3(high) activated/effector regulatory T cells in the CCR7 + CD45RA-CD27 + CD28+central memory subset are decreased in peripheral blood from patients with rheumatoid arthritis.
abstract: 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.
authors.affiliation: Department of Evidence-Based Laboratory Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Fumichika
authors.initials: F
authors.lastname: Matsuki
authors.forename: Jun
authors.initials: J
authors.lastname: Saegusa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Kenta
authors.initials: K
authors.lastname: Misaki
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kumagai
authors.forename: Akio
authors.initials: A
authors.lastname: Morinobu
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology; D018106:CD28 Antigens / Q000032:analysis* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7 / Q000032:analysis* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: C515370:CCR7 protein, human; D018106:CD28 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D054400:Receptors, CCR7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens
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