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

Min-Seok Rha; Sang-Wook Kim; Dong-Yeop Chang; Jin-Ku Lee; Jihye Kim; Su-Hyung Park; Roza Khalmuratova; Hee-Suk Lim; Kyoung Mi Eun; Seung-No Hong; Dae Woo Kim; Eui-Cheol Shin

doi:10.1016/j.jaci.2019.12.915

Superantigen-related T_H2 CD4⁺ T cells in nonasthmatic chronic rhinosinusitis with nasal polyps

J Allergy Clin Immunol. 2020 May;145(5):1378-1388.e10. doi: 10.1016/j.jaci.2019.12.915. Epub 2020 Jan 25.

Authors

Min-Seok Rha¹, Sang-Wook Kim², Dong-Yeop Chang³, Jin-Ku Lee⁴, Jihye Kim⁵, Su-Hyung Park⁶, Roza Khalmuratova⁷, Hee-Suk Lim⁸, Kyoung Mi Eun⁸, Seung-No Hong⁸, Dae Woo Kim⁹, Eui-Cheol Shin¹⁰

Affiliations

¹ Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
² Institute of Health Sciences, Gyeongsang National University, Jinju, Korea; Department of Otorhinolaryngology, Gyeongsang National University, Jinju, Korea.
³ Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea; Institute of Health Sciences, Gyeongsang National University, Jinju, Korea; Department of Otorhinolaryngology, Gyeongsang National University, Jinju, Korea.
⁴ Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, Korea.
⁵ BioMedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
⁶ Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea; BioMedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
⁷ Obstructive Upper Airway Research Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.
⁸ Department of Otorhinolaryngology-Head & Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
⁹ Department of Otorhinolaryngology-Head & Neck Surgery, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea. Electronic address: kicubi@daum.net.
¹⁰ Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea; BioMedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon, Korea. Electronic address: ecshin@kaist.ac.kr.

PMID: 31987845
DOI: 10.1016/j.jaci.2019.12.915

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.

Objective: We investigated the presence of SAEs and SAE-related T-cell receptor (TCR) Vβ (TCRVβ) 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 TCRVβ 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 TCRVβ⁺ (TCRVβ1⁺ and Vβ5.1⁺) CD4⁺ T cells was significantly increased only in NPs and the ethmoidal mucosa of patients with CRSwNP, indicating superantigen-induced expansion. The expanded TCRVβ5.1⁺ CD4⁺ T cells expressed proliferation marker Ki-67 and the T_H2 transcription factor GATA3. Furthermore, TCRVβ5.1⁺ CD4⁺ T cells in NPs highly expressed T_H2 markers, including IL-17RB, thymic stromal lymphoprotein receptor, and chemoattractant receptor-homologous molecule expressed on T_H2 cells, with a potent T_H2 cytokine-producing ability. Moreover, the expansion of TCRVβ1⁺ or Vβ5.1⁺ 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_H2 differentiation was associated with the disease extent.

Keywords: Chronic rhinosinusitis; Staphylococcus aureus enterotoxin; T cells; T(H)2; nasal polyp; superantigen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
CD4-Positive T-Lymphocytes / immunology*
Cell Differentiation
Chronic Disease
DNA, Bacterial / analysis
Enterotoxins / genetics
Enterotoxins / immunology*
Female
GATA3 Transcription Factor / immunology
Humans
Ki-67 Antigen / immunology
Male
Middle Aged
Nasal Polyps / immunology*
Proto-Oncogene Proteins c-bcl-2 / immunology
Receptors, Antigen, T-Cell / immunology
Rhinitis / immunology*
Sinusitis / immunology*
Superantigens / genetics
Superantigens / immunology*

Substances

BCL2 protein, human
DNA, Bacterial
Enterotoxins
GATA3 Transcription Factor
GATA3 protein, human
Ki-67 Antigen
MKI67 protein, human
Proto-Oncogene Proteins c-bcl-2
Receptors, Antigen, T-Cell
Superantigens