강인수 (Yale University School of Medicine)

한빛사논문

조회201

Yale University School of Medicine

EBioMedicine, Volume 103, May 2024, 105114 | https://doi.org/10.1016/j.ebiom.2024.105114 IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination

Hong-Jai Park ^a, Min Sun Shin ^a, Junghee J. Shin ^a, Hyoungsu Kim ^a,b, Byunghyun Kang ^c, Jennefer Par-Young ^a, Serhan Unlu ^a, Yuliya Afinogenova ^a, Jason Catanzaro^d, Juan Young^e, Minhyung Kim^f, Sang Jin Lee ^a,g, Sangchoon Jeon ^h, Sungyong You ^f, Michael K. Racke ⁱ, Richard Bucala ^a, Insoo Kang ^a

^aDepartment of Internal Medicine (Section of Rheumatology, Allergy & Immunology), Yale University School of Medicine, New Haven, CT, 06520, USA

^bDepartment of Internal Medicine, Hallym University School of Medicine, Chuncheon, Gangwon-do, 24252, South Korea

^cMucosal Immunology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA

^dSection of Pulmonary, Allergy, Immunology and Sleep Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, CT, 06520, USA

^eDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA

^fDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

^gDepartment of Internal Medicine, Kyungpook National University School of Medicine, Daegu, 41944, South Korea

^hYale University School of Nursing, West Haven, CT, 06516, USA

ⁱQuest Diagnostics, 500 Plaza Dr, Secaucus, NJ, 07094, USA

Corresponding author : Insoo Kang

Abstract

Background: The innate immune cytokine interleukin (IL)-1 can affect T cell immunity, a critical factor in host defense. In a previous study, we identified a subset of human CD4+ T cells which express IL-1 receptor 1 (IL-1R1). However, the expression of such receptor by viral antigen-specific CD4+ T cells and its biological implication remain largely unexplored. This led us to investigate the implication of IL-1R1 in the development of viral antigen-specific CD4+ T cell responses in humans, including healthy individuals and patients with primary antibody deficiency (PAD), and animals.

Methods: We characterized CD4+ T cells specific for SARS-CoV-2 spike (S) protein, influenza virus, and cytomegalovirus utilizing multiplexed single cell RNA-seq, mass cytometry and flow cytometry followed by an animal study.

Findings: In healthy individuals, CD4+ T cells specific for viral antigens, including S protein, highly expressed IL-1R1. IL-1β promoted interferon (IFN)-γ expression by S protein-stimulated CD4+ T cells, supporting the functional implication of IL-1R1. Following the 2nd dose of COVID-19 mRNA vaccines, S protein-specific CD4+ T cells with high levels of IL-1R1 increased, likely reflecting repetitive antigenic stimulation. The expression levels of IL-1R1 by such cells correlated with the development of serum anti-S protein IgG antibody. A similar finding of increased expression of IL-1R1 by S protein-specific CD4+ T cells was also observed in patients with PAD following COVID-19 mRNA vaccination although the expression levels of IL-1R1 by such cells did not correlate with the levels of serum anti-S protein IgG antibody. In mice immunized with COVID-19 mRNA vaccine, neutralizing IL-1R1 decreased IFN-γ expression by S protein-specific CD4+ T cells and the development of anti-S protein IgG antibody.

Interpretation: Our results demonstrate the significance of IL-1R1 expression in CD4+ T cells for the development of viral antigen-specific CD4+ T cell responses, contributing to humoral immunity. This provides an insig

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-04-22)
연구진국외 연구진
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