Background: Staphylococcus aureus enterotoxin (SAE) superantigens are detected in nasal polyps (NPs), and SAE-specific IgE predicts asthma comorbidity in patients with NPs. However, roles of SAE superantigens and superantigen-related T-cell responses remain to be elucidated in nonasthmatic patients. Objective: We investigated the presence of SAEs and SAE-related T-cell receptor (TCR) V beta (TCRV beta) in nonasthmatic NPs, the phenotypes and functions of SAE-related T cells, and the clinical implication of SAE-related T-cell expansion. Methods: Sinonasal tissue samples were obtained from patients with nonasthmatic chronic rhinosinusitis (CRS) with NPs (CRSwNP), patients with CRS without NPs (CRSsNP), and control subjects. SAE genes were detected by PCR, and the TCRV beta distribution and T-cell phenotypes were examined by flow cytometry. Results: Various SAE genes were detected not only in NPs but also in sinonasal mucosa from patients with CRSsNP and from controls. The S aureus enterotoxin I (SEI) gene was detected in all NPs. The fraction of SEI-responsive TCRV beta(+) (TCRV beta 1(+) and V beta 5.1(+)) CD4(+) T cells was significantly increased only in NPs and the ethmoidal mucosa of patients with CRSwNP, indicating superantigen-induced expansion. The expanded TCRV beta 5.1(+) CD4(+) T cells expressed proliferation marker Ki-67 and the T(H)2 transcription factor GATA3. Furthermore, TCRV beta 5.1(+) CD4(+) T cells in NPs highly expressed T(H)2 markers, including IL-17RB, thymic stromal lymphoprotein receptor, and chemoattractant receptor-homologous molecule expressed on T(H)2 cells, with a potent T(H)2 cytokine-producing ability. Moreover, the expansion of TCRV beta 1(+) or V beta 5.1(+) CD4(+) T cells was associated with the Lund-Mackay computed tomography score, indicating disease extent. Conclusion: In nonasthmatic patients with CRSwNP, superantigen-related expansion of CD4(+) T cells with T(H)2 differentiation was associated with the disease extent.