Role of CD8+ T cell exhaustion in the progression and prognosis of acute respiratory distress syndrome induced by sepsis: a prospective observational study
Lei Yan, Yumei Chen, Yi Han, Chaoyang Tong
Abstract
Abstract 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.