Superantigen-related TH2 CD4(+) T cells in nonasthmatic chronic rhinosinusitis with nasal polyps

Abstract

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. <br>OBJECTIVE: We investigated the presence of SAEs and SAE-related T-cell receptor (TCR) Vbeta (TCRVbeta) in nonasthmatic NPs, the phenotypes and functions of SAE-related T cells, and the clinical implication of SAE-related T-cell expansion. <br>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 TCRVbeta distribution and T-cell phenotypes were examined by flow cytometry. <br>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 TCRVbeta(+) (TCRVbeta1(+) and Vbeta5.1(+)) CD4(+) T cells was significantly increased only in NPs and the ethmoidal mucosa of patients with CRSwNP, indicating superantigen-induced expansion. The expanded TCRVbeta5.1(+) CD4(+) T cells expressed proliferation marker Ki-67 and the TH2 transcription factor GATA3. Furthermore, TCRVbeta5.1(+) CD4(+) T cells in NPs highly expressed TH2 markers, including IL-17RB, thymic stromal lymphoprotein receptor, and chemoattractant receptor-homologous molecule expressed on TH2 cells, with a potent TH2 cytokine-producing ability. Moreover, the expansion of TCRVbeta1(+) or Vbeta5.1(+) CD4(+) T cells was associated with the Lund-Mackay computed tomography score, indicating disease extent. <br>CONCLUSION: In nonasthmatic patients with CRSwNP, superantigen-related expansion of CD4(+) T cells with TH2 differentiation was associated with the disease extent.