Superantigen-related Th2 CD4+ T Cells in Non-asthmatic Chronic Rhinosinusitis with Nasal Polyps

Abstract Background Staphylococcus aureus enterotoxin (SAE) superantigens are detected in nasal polyps (NPs), and SAE-specific immunoglobulin E predicts asthma comorbidity in patients with NPs. However, roles of SAE superantigens and superantigen-related T-cell responses remain to be elucidated in non-asthmatic patients. Objective We investigated the presence of SAEs and SAE-related T cell receptor (TCR) Vβ in non-asthmatic NPs, the phenotypes and functions of SAE-related T cells, and the clinical implication of SAE-related T-cell expansion. Methods Sinonasal tissues were obtained from patients with non-asthmatic chronic rhinosinusitis (CRS) with (CRSwNP) or without NP (CRSsNP) and control subjects. SAE genes were detected by polymerase chain reaction and the TCRVβ distribution and T-cell phenotypes examined by flow cytometry. Results Various SAE genes were detected not only in NPs but also in sinonasal tissues of CRSsNP patients and controls. The S. aureus enterotoxin I (SEI) gene was detected in all NPs. The fraction of SEI-responsive TCRVβ+ (TCRVβ1+ and Vβ5.1+) CD4+ T cells was significantly increased only in NPs and ethmoidal mucosal tissues from CRSwNP patients, indicating superantigen-induced expansion. The expanded TCRVβ5.1+ CD4+ T cells expressed proliferation marker Ki-67 and the Th2 transcription factor GATA3. Furthermore, TCRVβ5.1+ CD4+ T cells in NPs highly expressed Th2 markers, including IL-17RB, TSLPR, and CRTH2, with a potent Th2 cytokine-producing ability. Moreover, the expansion of TCRVβ1+ or Vβ5.1+ CD4+ T cells was associated with the Lund-Mackay CT score, indicating disease extent. Conclusion In non-asthmatic CRSwNP patients, superantigen-related expansion of CD4+ T cells with Th2 differentiation was associated with the disease extent.