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

tetano

Editor, Senior Moderator
Nat Commun


. 2025 Nov 27.
doi: 10.1038/s41467-025-66753-1. Online ahead of print. Dysregulation of homeostatic cytokine receptors drives prolonged T cell activation following acute SARS-CoV-2 infection in humans

Laura Ceglarek[SUP] 1 2 3 [/SUP], Patrick Taeschler[SUP] 2 [/SUP], Alp Inci[SUP] 1 2 [/SUP], Yves Zurbuchen[SUP] 1 2 [/SUP], Sarah Adamo[SUP] 2 [/SUP], Carlo Cervia-Hasler[SUP] 2 [/SUP], Miro E Raeber[SUP] 1 2 3 4 [/SUP], Onur Boyman[SUP] 5 6 7 8 9 [/SUP]



Affiliations
Abstract

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[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.


 
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