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<p>Acute viral infections are usually cleared by an efficient anti-pathogen immune response, following which immune homeostasis is restored. Occasionally, such pathogen-induced immune response fails to abate despite clinical recovery, but how this occurs in humans has not been thoroughly investigated. Here, we perform a detailed analysis of T cell homeostasis following&#xa0;severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which reveals persistent activation and dyshomeostasis of CD4<sup>+</sup> and CD8<sup>+</sup> T cells for 6–12 months after acute infection. Compared to steady-state and unlike T cell responses following vaccination, interleukin (IL)−2 receptor and IL-7 receptor expression remains altered on both SARS-CoV-2-specific and bystander T cells for 6–12 months after acute infection. These alterations correlate with increased IL-7 and IL-15 serum levels and are reproduced by in vitro stimulation by IL-7 and IL-15, but surprisingly not by IL-2. Collectively, our study demonstrates prolonged T cell dyshomeostasis driven by dysregulated homeostatic cytokine signals following acute viral infection.</p>

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Dysregulation of homeostatic cytokine receptors drives prolonged T cell activation following acute SARS-CoV-2 infection in humans

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月27日

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  • Laura Ceglarek,
  • Patrick Taeschler,
  • Alp Inci,
  • Yves Zurbuchen,
  • Sarah Adamo,
  • Carlo Cervia-Hasler,
  • Miro E. Raeber,
  • Onur Boyman

摘要

Acute viral infections are usually cleared by an efficient anti-pathogen immune response, following which immune homeostasis is restored. Occasionally, such pathogen-induced immune response fails to abate despite clinical recovery, but how this occurs in humans has not been thoroughly investigated. Here, we perform a detailed analysis of T cell homeostasis following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which reveals persistent activation and dyshomeostasis of CD4+ and CD8+ T cells for 6–12 months after acute infection. Compared to steady-state and unlike T cell responses following vaccination, interleukin (IL)−2 receptor and IL-7 receptor expression remains altered on both SARS-CoV-2-specific and bystander T cells for 6–12 months after acute infection. These alterations correlate with increased IL-7 and IL-15 serum levels and are reproduced by in vitro stimulation by IL-7 and IL-15, but surprisingly not by IL-2. Collectively, our study demonstrates prolonged T cell dyshomeostasis driven by dysregulated homeostatic cytokine signals following acute viral infection.