Increased apoptosis induction in CD4+ CD25+ Foxp3+ T cells contributes to enhanced disease activity in patients with rheumatoid arthritis through IL-10 regulation.
BACKGROUND
Abnormality in the number and function of regulatory T cells (Tregs) has been linked to initiation and progression in patients with Rheumatoid Arthritis (RA).


OBJECTIVE
This study aims to demonstrate the apoptosis status of regulatory T cells (Tregs) and its correlation with clinical activity of RA patients and the effect of interleukin-10 (IL-10) on Tregs apoptosis in RA.


METHODS
Apoptosis rates and its related molecules including Fas, Bcl-2, Caspase-3 and Caspase-8 were examined using flow cytometry. The correlation between the apoptosis level of Tregs and clinical activity parameters including ESR (erythrocyte sedimentation rate), CPR (C reactive protein), RF (Rheumatoid Factor) and DAS28 (Disease activity score 28) was analysed. PBMCs isolated from RA patients were cultured with IL-10 or anti-IL-10, and the apoptosis frequency of Tregs was then analyzed.


RESULTS
The frequency of Tregs in active RA patients was decreased, and Fas, Caspase-3 and Caspase-8 expression on Tregs was much higher compared with the healthy subjects. The expression of anti-apoptotic protein, Bcl-2 on Tregs did not display significant changes between active RA patients and healthy subjects. There was a significantly positive correlation between the levels of apoptosis rates and Caspase-3 expression in Tregs and DAS28 of active RA patients. The apoptosis rates of Tregs in RA patients decreased or increased, respectively, following treatment with IL-10 or anti-IL-10 antibody in vitro.


CONCLUSIONS
Apoptosis pathways are defective in Treg cells from RA patients with active disease. IL-10 treatment can modulate apoptosis in Tregs via extrinsic (type I) pathway, which may lead to restoration of the Tregs towards that of controlling autoimmune reaction in RA patients.
Department of Rheumatology, Tong Ji University Affiliated Shanghai East Hospital, Shanghai, China. hjgj85528@sina.com.
N
N
Li
T
T
Ma
J
J
Han
J
J
Zhou
J
J
Wang
J
J
Zhang
S
S
Zheng
D000328:Adult; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D053148:Caspase 3 / Q000276:immunology; D053181:Caspase 8 / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D019014:fas Receptor; D016753:Interleukin-10; D053148:Caspase 3; D053181:Caspase 8