The role of T cells in sepsis of distinct infectious aetiologies

Abstract Sepsis is a complex and life‐threatening syndrome resulting from infection and characterized by dysregulated host immune responses. T cells play a central role in orchestrating immune defence against pathogens, yet their function undergoes profound alterations during sepsis. The impact of sepsis on T cell function varies depending on the causative pathogen. T cells exhibit an initial hyperactivation phase in bacterial sepsis, followed by a state of exhaustion, characterised by reduced cytokine production, impaired proliferation, and metabolic dysfunction. Such disorders are associated with disruptions in T cell receptor signalling, upregulation of immune checkpoint molecules such as PD‐1 and CTLA4, and mitochondrial damage. T cell dysfunction is often linked to immunosuppression in viral sepsis, with an inhibition of antiviral responses and induction of immune tolerance. The distinct immune evasion strategies impair T cell‐mediated pathogen clearance in viral sepsis, while altered T cell subsets are observed in fungal and parasitic sepsis. Such immune dysregulations exacerbate sepsis‐induced immune suppression, increase susceptibility to secondary infections, and worsen clinical outcomes. Elucidating the pathogen‐specific pathways that underlie T cell dysfunction in sepsis is crucial for the development of precise immunotherapies. These insights could inform the design of therapeutic strategies aimed at restoring T cell function and improving the prognosis of septic patients.