CD4+CD25high T cell numbers are enriched in the peripheral blood of patients with rheumatoid arthritis.
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.
Han
Guang Ming
GM
Biggs Laboratory, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201-0509, USA.
O'Neil-Andersen
Nancy J
NJ
Zurier
Robert B
RB
Lawrence
David A
DA
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
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