Stimulation Of Alpha 7 Nicotinic Acetylcholine Receptor By Nicotine Increases Suppressive Capacity Of Naturally Occurring Cd4(+)Cd25(+) Regulatory T Cells In Mice In Vitro

alpha 7 Nicotinic acetylcholine receptor (alpha 7 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 alpha 7 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 alpha 7 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-beta 1 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)-gamma, which partially represented T-cell polarization. The above-mentioned effects of nicotine were reversed by a selective alpha 7 nAChR antagonist, alpha-bungarotoxin. In addition, the ratio of IL-4/IFN-gamma was increased by treatment with alpha-bungarotoxin. We conclude that nicotine might increase Treg-mediated immune suppression of lymphocytes via alpha 7 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. alpha 7 nAChR seems to be a critical regulator for immunosuppressive function of CD4(+)CD25(+) Tregs.