Reduced number and function of CD4+CD25highFoxP3+ regulatory T cells in patients with systemic lupus erythematosus.
CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining tolerance to self-antigens controlling occurrence of autoimmune diseases. Recently, it has been shown that the transcription factor forkhead box P3 (FoxP3) is specifically expressed on CD4+CD25+ T cells. FoxP3 has been described as the master control gene for the development and function of Tregs. We characterized CD4+CD25+CTLA-4+FoxP3+ T cells in 43 patients with systemic lupus erythematosus (SLE). Twenty of them comprised a group of newly admitted patients with the first manifestations of the disease, and the second group included patients that were treated with cytostatics and steroids. The results revealed a significant decrease in CD4+CD25+ and CD4+CD25high T cells numbers in patients from group I compared with control and group II patients. Coexpression of FoxP3 on CD4+CD25+ T cells was significantly reduced in both groups regardless the therapy. The ability of Tregs to suppress proliferation of autologous CD8+ and CD4+ T cells was significantly reduced in both groups of patients compared to healthy donors. Our data revealed impaired production of Tregs in SLE patients that can be partly restored by conventional treatments.
Lyssuk
Elena Yu
EY
Laboratory of Cell Monitoring, Institution of Rheumatology, Russian Academy of Medical Sciences, Moscow, Russia.
Torgashina
Anna V
AV
Soloviev
Sergey K
SK
Nassonov
Evgeny L
EL
Bykovskaia
Svetlana N
SN
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D060908:CTLA-4 Antigen; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit