Rethinking IL-1 Antagonism in Respiratory Viral Infections: A Role for IL-1 Signaling in the Development of Antiviral T Cell Immunity

Abstract

IL-1R integrates signals from IL-1α and IL-1β, and it is widely expressed across tissues and immune cell types. While the expression pattern and function of IL-1R within the innate immune system is well studied, its role in adaptive immunity, particularly within the CD8 T cell compartment, remains underexplored. Here, we show that CD8 T cells dynamically upregulate IL-1R1 levels during priming by APCs, which correlates with their proliferation status and the acquisition of an effector phenotype. Notably, this IL-1 sensitivity persists in memory CD8 T cells of both mice and humans, influencing effector cytokine production upon TCR reactivation. Furthermore, our study highlights that antiviral effector and tissue-resident CD8 T cell responses against influenza A virus infection become impaired in the absence of IL-1 signaling. Altogether, these data support the exploitation of IL-1 activity in the context of T cell vaccination strategies and warrant consideration of the impact of clinical IL-1 inhibition on the rollout of T cell immunity.

Editorial for the Special Issue “Cytokines in Inflammatory Signaling”

“…These articles not only further our appreciation of the systemic nature of cytokine activity but also emphasize the translational potential of cytokine research in enhancing athletic performance and managing chronic diseases. Lastly, the brief report on IL-1 signaling in antiviral T cell immunity challenges us to reconsider the role of IL-1 in the context of infectious diseases and vaccination strategies [ 10 ]. This piece, in particular, underscores the delicate balance between cytokine-mediated protection and pathology, a recurring theme throughout this Special Issue.…”