Roth Georg, Moser Bernhard, Krenn Claus, Brunner Markus, Haisjackl Markus, Almer Gabriele, Gerlitz Sabine, Wolner Ernst, Boltz-Nitulescu George, Ankersmit Hendrik J
Department of Surgery, General Hospital of Vienna Medical School, Vienna, Austria.
Biochem Biophys Res Commun. 2003 Sep 5;308(4):840-6. doi: 10.1016/s0006-291x(03)01482-7.
Sepsis causes lymphopenia which is inversely correlated with patient survival. The role of apoptosis-specific immune-activation and activation-induced cell-death in sepsis is incompletely understood. Fifteen septic patients and 20 healthy controls were included. T-cell proliferation was measured by [3H]thymidine uptake. Apoptosis and cell phenotype were determined by FACS. sTNFR1, sCD95, interleukin-1beta converting enzyme (sICE), and interleukin (IL)-10 were measured by ELISA. PHA and CD3-driven T-cell proliferation were significantly decreased in septic patients. The percentages of CD3(+) and CD4(+) T cells and CD19(+) B cells were significantly reduced. Percent memory T-cells (CD45RO(+)) and cells undergoing apoptosis (CD95(+)/annexin-V(+)) were significantly increased in sepsis. Moreover, sCD95, sTNFRI, and ICE were significantly increased. Anti-CD3 antibody triggering induced a 56% increase of CD4 T-cell death in septic patients vs. 7.5% in controls relative to IgG. Serum level of IL-10, a Th2 cytokine, was enhanced. These findings strongly suggest that in septic patients Th1 T-cells are selectively susceptible to undergo apoptosis. This observation provides an additional pathophysiological concept in the genesis of Th2 dominance.
脓毒症可导致淋巴细胞减少，而淋巴细胞减少与患者生存率呈负相关。凋亡特异性免疫激活和激活诱导的细胞死亡在脓毒症中的作用尚未完全明确。研究纳入了15例脓毒症患者和20例健康对照。通过[3H]胸苷摄取来测量T细胞增殖。通过流式细胞术确定细胞凋亡和细胞表型。采用酶联免疫吸附测定法检测可溶性肿瘤坏死因子受体1（sTNFR1）、可溶性CD95（sCD95）、白细胞介素-1β转化酶（sICE）和白细胞介素（IL）-10。脓毒症患者中，由植物血凝素（PHA）和CD3驱动的T细胞增殖显著降低。CD3(+)和CD4(+) T细胞以及CD19(+) B细胞的百分比显著降低。脓毒症患者中记忆T细胞（CD45RO(+)）百分比和发生凋亡的细胞（CD95(+)/膜联蛋白-V(+)）百分比显著增加。此外，sCD95、sTNFRI和ICE显著升高。相对于IgG，抗CD3抗体触发导致脓毒症患者CD4 T细胞死亡增加56%，而对照组为7.5%。Th2细胞因子IL-10的血清水平升高。这些发现强烈表明，脓毒症患者中Th1 T细胞对凋亡具有选择性易感性。这一观察结果为Th2优势的发生提供了另一种病理生理学概念。
