Roles of PD-1, Tim-3 and CTLA-4 in immunoregulation in regulatory T cells among patients with sepsis.

Objective: This study aims to elucidate the roles of PD-1, Tim-3 and CTLA-4 in sepsis.

Methods: Sepsis patients (n = 182) were selected as sepsis group and divided into three subgroups: mild sepsis group, severe sepsis group and septic shock group; 185 healthy volunteers were enrolled as control group. Flow cytometry and blood routine examination were performed for T lymphocytes and surface co-stimulatory molecules expressions. Pearson correlation test was applied for the correlation of co-stimulatory molecules expressions on T lymphocytes with critical illness in sepsis. Logistic regression analysis was conducted for risk factors in sepsis.

Results: Heart rate and WBC in subgroups were higher than control group (P < 0.05). The differences in APACHE II, SAP II and SOFA score among subgroups were statistically significant (P < 0.05). Compared with control group, lymphocyte ratio and percentage of CD4(+) T cells reduced in subgroups (P < 0.05). The differences in expression levels of CD4(+)PD-1(+), CD8(+)PD-1(+), and CD8(+)CTLA-4(+) showed statistical significances (P < 0.05). Apparently, expression levels of CD4(+)TIM-3(+), CD8(+)TIM-3(+), CD4(+)PD-1(+), CD8(+)PD-1(+), and CD4(+)CTLA-4(+) were positively correlated with APACHE II score (all P < 0.05). Logistic regression analysis showed that heart rate and expression level of CD4(+)PD-1(+) might be risk factors while the percentage of CD4(+) T cells might be a protective factor for sepsis (P < 0.05).

Conclusion: PD-1 aggravates immune responses consistent with promotion of T cell exhaustion in sepsis. Expression level of CD4(+)PD-1(+) and heart rate are potential risk factors while percentage of CD4(+) T cells is a possible protective factor for sepsis.