摘要目的:探讨脓毒症患者外周血CD4 ＋T淋巴细胞的免疫表型特征。 方法:本研究为纵向队列研究。纳入2020年9月1日至2021年1月31日复旦大学附属华山医院和太仓市第一人民医院收治的51例感染性疾病患者，分为感染组(30例)与脓毒症组(21例)。收集患者临床资料及外周血样本，采用高参数多色流式细胞术检测外周血CD4 ＋T淋巴细胞表面活化和共抑制分子的表达。比较感染组和脓毒症组的临床资料、实验室检查结果、CD4 ＋T淋巴细胞表面功能分子。统计学分析采用 χ2检验和曼-惠特尼 U检验。 结果:感染组与脓毒症组患者年龄、性别、体重指数、病程差异无统计学意义(均 P>0.05)。脓毒症组序贯器官衰竭评估评分及C反应蛋白、降钙素原高于感染组，而淋巴细胞计数、血小板计数低于感染组，差异均有统计学意义( U＝7.00、145.50、163.50、178.50、142.00，均 P<0.05)。在CD4 ＋T淋巴细胞表面分子表达方面，脓毒症组CD25、趋化因子CXC亚家族受体5(CXCR5)表达水平[19.00(15.15，30.25)%和15.40(8.79，20.15)%]低于感染组[25.95(20.95，33.78)%和19.40(16.43，23.50)%]，程序性死亡蛋白-1(PD-1)、CD39、T细胞免疫球蛋白黏蛋白3(TIM3)表达水平[30.70(22.90, 49.70)%、7.80(3.01，15.45)%和1.56(0.86，6.57)%]分别高于感染组[25.65(18.98，32.78)%、2.73(1.45，8.78)%和0.78(0.37，2.55)%]，差异均有统计学意义( U＝187.00、211.00、212.00、89.00、212.50，均 P<0.05)。亚群分析显示，脓毒症组PD-1 －KLRG1 ＋(KLRG1为杀伤细胞凝集素样受体G1)与PD-1 －TIGIT ＋(TIGIT为T细胞免疫球蛋白和免疫受体酪氨酸抑制模体结构域蛋白)亚群比例[2.13(1.19，3.97)%和7.09(4.34，8.82)%]低于感染组[4.10(2.62，5.71)%和10.10(6.85，11.68)%]( U＝188.50、205.00，均 P<0.05)。 结论:脓毒症患者CD4 ＋T淋巴细胞呈现特征性免疫功能障碍，表现为活化受损与耗竭增强并存，具体特征为活化分子CD25、CXCR5表达下降而共抑制分子PD-1、CD39、TIM3表达上调。相关分子及亚群的变化可为脓毒症的研究及临床诊疗提供参考。

abstractsObjective:To investigate the immunophenotypic characteristics of CD4 + T lymphocytes in the peripheral blood of patients with sepsis. Methods:This study was a longitudinal cohort study. A total of 51 patients with infectious diseases admitted to Huashan Hospital, Fudan University and the First People′s Hospital of Taicang from September 1st, 2020 to January 31st, 2021 were enrolled and divided into infection group (30 cases) and sepsis group (21 cases). Clinical data and peripheral blood samples were collected. High-parameter multicolor flow cytometry was used to detect the expressions of surface activated and co-inhibitory molecules on CD4 + T lymphocytes. The clinical data, laboratory test results and surface functional molecules of CD4 + T lymphocyte between the infection group and the sepsis group were compared. Chi-square test and Mann-Whitney U test were used for statistical analysis. Results:No significant differences in age, gender, body mass index or disease course were observed between the infection group and the sepsis group (all P>0.05). The sequential organ failure assessment scores, C-reactive protein and procalcitonin in the sepsis group were significantly higher than those in the infection group, whereas the lymphocyte count and platelet count were significantly lower ( U=7.00, 145.50, 163.50, 178.50 and 142.00, respectively, all P<0.05). In terms of the expressions of surface molecules on CD4 + T lymphocytes, the expression levels of CD25 and CXC subfamily receptor 5(CXCR5) in the sepsis group (19.00(15.15, 30.25)% and 15.40(8.79, 20.15)%) were significantly lower than those in the infection group(25.95(20.95, 33.78)% and 19.40(16.43, 23.50)%), while the expression levels of programmed cell death protein 1 (PD-1) (30.70(22.90, 49.70)% vs 25.65(18.98, 32.78)%), CD39(7.80(3.01, 15.45)% vs 2.73(1.45, 8.78)%), and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3)(1.56(0.86, 6.57)% vs 0.78(0.37, 2.55)%) were significantly higher ( U=187.00, 211.00, 212.00, 89.00, 212.50, all P<0.05). Subset analysis revealed that the proportions of PD-1 - KLRG1 + ( KLRG1 is killer cell lectin-like receptor G1) and PD-1 -TIGIT + (TIGIT is T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) subsets in the sepsis group (2.13(1.19, 3.97)% and 7.09(4.34, 8.82)%) were both significantly lower than those in the infection group (4.10(2.62, 5.71)% and 10.10(6.85, 11.68)%) ( U=188.50, 205.00, both P<0.05). Conclusions:T lymphocytes in sepsis patients exhibit characteristic immune dysfunction, marked by impaired activation and enhanced exhaustion, specifically characterized by decreased expressions of activated molecules CD25 and CXCR5 and increased expressions of co-inhibitory molecules PD-1, CD39 and TIM3. The alterations in related molecules and subsets may provide valuable insights for sepsis research and clinical diagnosis and treatment.