Role of CD8+ T cell exhaustion in the progression and prognosis of acute respiratory distress syndrome induced by sepsis: a prospective observational study

Background:CD8⁺ T cells are important for protective immunity against intracellular pathogens. Excessive amounts of antigen and/or inflammatory signals often lead to the gradual deterioration of CD8⁺ T cell function, a state called "exhaustion". However, the association between CD8⁺ T cell exhaustion and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how CD8⁺ T cells and inhibitory receptors were related to the clinical prognosis of ARDS.

Methods:A prospective observational study in an emergency department enrolled patients who were diagnosed with sepsis-associated ARDS according to the sepsis-3 criteria and Berlin definition. Peripheral blood samples were collected within 24 h post recruitment. CD8⁺ T cell count, proliferation ratio, cytokine secretion, and the expression of coinhibitory receptors were assayed.

Results:Sixty-two patients with ARDS met the inclusion criteria. CD8⁺ T cell counts and proliferation rates were dramatically decreased in non-surviving ARDS patients. Increasing programmed cell death 1 (PD-1) expression on the CD8⁺ T cell surface was seen in patients with worse organ function, while an increasing level of T cell immunoglobulin mucin-3 (Tim-3) was associated with a longer duration of the shock. Kaplan-Meier analysis showed that low CD8⁺ T cell percentages and increased inhibitory molecule expression were significantly associated with a worse survival rate.

Conclusions:CD8⁺ T cells and coinhibitory receptors are promising independent prognostic markers of sepsis-induced ARDS, and increased CD8⁺ T cell exhaustion is significantly correlated with poor prognosis.

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