Accumulating evidence has demonstrated that naturally occurring CD4(+)CD25(+) 
regulatory T cells (Tregs) are critical for maintenance of immunological 
tolerance and have been shown to be important in regulating the immune responses 
in many diseases. Curcumin, a phytochemical obtained from the rhizome of the 
plant Curcuma longa, has achieved the potential therapeutic interest to numerous 
immune-related disorders. However, the effect and mechanism of curcumin on Tregs 
remain largely elusive. In the present study, curcumin inhibition of the 
suppressive activity of CD4(+)CD25(+) regulatory T cells appears to be dependent 
on three categories: inhibiting cell-cell contact by down-regulation of CTLA-4, 
suppressing inhibitory cytokine secretion and decreasing the ability to consume 
IL-2 and/or suppress IL-2 production. In addition, Foxp3 expression was also 
reduced on Tregs after curcumin stimulation. Moreover, we found that nuclear 
translocation of p65 and c-Rel, which is critical for Foxp3 and CD25 
expressions, was markedly decreased in Tregs with curcumin stimulation. Based on 
the role of curcumin in the suppressive activity of Tregs, it may be feasible to 
use curcumin as an immunotherapy for Treg-related diseases, such as tumors and 
sepsis.