α7 Nicotinic acetylcholine receptor (α7 nAChR) has been found in several 
non-neuronal cells and is described as an important regulator of cellular 
function. Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) are 
essential for the active suppression of autoimmunity. The present study 
investigated whether naturally occurring Tregs expressed α7 nAChR and 
investigated the functionary role of this receptor in controlling suppressive 
activity of these cells. We found that CD4(+)CD25(+) Tregs from naive C57BL/6J 
mice positively expressed α7 nAChR, and its activation by nicotine enhanced the 
suppressive capacity of Tregs. Nicotine stimulation up-regulated the expression 
of cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and forkhead/winged helix 
transcription factor p3 (Foxp3) on Tregs but had no effect on the production of 
interleukin (IL)-10 and transforming growth factor-β1 by Tregs. In the 
supernatants of CD4(+)CD25(+) Tregs/CD4(+)CD25(-) T-cell cocultures, we observed 
a decrease in the concentration of IL-2 in nicotine-stimulated groups, but 
nicotine stimulation had no effect on the ratio of IL-4/interferon (IFN)-γ, 
which partially represented T-cell polarization. The above-mentioned effects of 
nicotine were reversed by a selective α7 nAChR antagonist, α-bungarotoxin. In 
addition, the ratio of IL-4/IFN-γ was increased by treatment with 
α-bungarotoxin. We conclude that nicotine might increase Treg-mediated immune 
suppression of lymphocytes via α7 nAChR. The effect is related to the 
up-regulation of CTLA-4 as well as Foxp3 expression and decreased IL-2 secretion 
in CD4(+)CD25(+) Tregs/CD4(+)CD25(-) T-cell coculture supernatants. α7 nAChR 
seems to be a critical regulator for immunosuppressive function of CD4(+)CD25(+) 
Tregs.