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).

AIM

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.

MATERIALS AND 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.