Objective · To investigate the effect of sublingual immunotherapy (SLIT) on the functions of effector T cells (Teff) and regulatory T cells (Treg) under allergic rhinitis (AR) condition. Methods · Peripheral blood mononuclear cells (PBMC) were obtained from 20 AR patients who were recruited from Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital North of Fudan University before and after the 24- and 30-month treatments of SLIT. The percentages of Teff and Treg in CD4+ T cells in PBMC were examined and the contents of calcium release-activated calcium channel modulator 1 (ORAI1) protein and Ca2+ mean fluorescence intensity (MFI) in PBMC were measured. Then, Teff and Treg after the 30-month treatment were cultured in vitro, and were evaluated for the expression of ORAI1 protein and concentrations of interleukin-4 (IL-4) and IL-10 in the cultures. Lentivirus vector (lenti) that encoded short hairpin RNA against ORAI1 (lenti-ORAI1) was prepared and transfected into Teff and Treg, and then Ca2+ MFI in Teff and Treg and concentrations of IL-4 and IL-10 in the cultures were assessed again. Results · The percentage of Teff in CD4+ T cells in PBMC reduced gradually after the 24- and 30-month treatments (P=0.000, P=0.027); however, the percentage of Treg was increased (P=0.000, P=0.008). The expression of ORAI1 protein (P=0.000, P=0.003) and Ca2+ MFI (P=0.000, P=0.000) in Teff were also decreased gradually after the 24- and 30-month treatments; however, the expression of ORAI1 protein (P=0.000, P=0.007) and Ca2+ MFI in Treg were enhanced (P=0.000, P=0.000). ORAI1 protein was expressed in these two types of cells cultured in vitro. Furthermore, Ca2+ MFI in them (P=0.004, P=0.000) and IL-4 (P=0.009) and IL-10 (P=0.000) in the cultures were all decreased after the transfection of lenti-ORAI1. Conclusion · SLIT can control functions of Teff and Treg through regulating the expression of ORAI1 protein.