title: CD4+CD25high T cell numbers are enriched in the peripheral blood of patients with rheumatoid arthritis.
abstract: Accumulating evidences support that CD4(+)CD25(high) T regulatory (Treg) cells play an essential role in controlling and preventing autoimmunity. Paradoxically, RA patients have elevated numbers of circulating CD4(+)CD25(high) T cells, however, the inflammation is still ongoing. Further identification of these CD4(+)CD25(high) T cells may contribute to a better understanding of underlying mechanisms. We show here that these CD4(+)CD25(high) T cells were composed of CD4(+)CD25(high)FoxP3(+) Treg cells and activated CD4(+)CD25(high)FoxP3(-) effector cells. Moreover, there were significantly more Treg cells and effector T cells expressing GITR, and more monocytes expressing GITR-L. Thus, although RA patients have elevated numbers of CD4(+)CD25(high) T cells, the suppressive function is not increased, because of the increased number of activated effector T cells. In addition, the GITR-GITR-L system was activated in RA patients, which might lead to diminish suppressive activity of Treg cells and/or lead to resistance of activated effector T cells to suppression by Treg cells, thus, contributing to the ongoing inflammation in RA patients.
authors.affiliation: Biggs Laboratory, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201-0509, USA.
authors.forename: Guang Ming
authors.initials: GM
authors.lastname: Han
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: O'Neil-Andersen
authors.forename: Robert B
authors.initials: RB
authors.lastname: Zurier
authors.forename: David A
authors.initials: DA
authors.lastname: Lawrence
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D048069:Tumor Necrosis Factors / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; C478967:TNFSF18 protein, human; D048069:Tumor Necrosis Factors