title: 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.
authors.affiliation: Department of Biotechnology, Immunology Division, University of Alicante, Alicante, Spain. josemiguel@ua.es
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Sempere-Ortells
authors.forename: Vicente
authors.initials: V
authors.lastname: Pérez-García
authors.forename: Gema
authors.initials: G
authors.lastname: Marín-Alberca
authors.forename: Alejandra
authors.initials: A
authors.lastname: Peris-Pertusa
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Benito
authors.forename: Francisco Manuel
authors.initials: FM
authors.lastname: Marco
authors.forename: José Jacobo
authors.initials: JJ
authors.lastname: Zubcoff
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Navarro-Blasco
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D018791:CD4 Lymphocyte Count; D060908:CTLA-4 Antigen; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate