Jooss Tobias, Maier Katharina, Reichardt Lena-Marie, Hindelang Bianca, Süberkrüb Lönna, Hamberger Kim Lena, Bülow Jasmin Maria, Schuetze Konrad, Gebhard Florian, Mannes Marco, Halbgebauer Rebecca, Wohlgemuth Lisa, Huber-Lang Markus, Relja Borna, Bergmann Christian B
Translational and Experimental Trauma Research, Department of Trauma-, Hand-, Plastic- and Reconstructive Surgery, Ulm University Medical Center, Ulm, Germany.
Department of Trauma-, Hand-, Plastic- and Reconstructive Surgery, Ulm University Medical Center, Ulm, Germany.
Front Immunol. 2025 Mar 24;16:1538516. doi: 10.3389/fimmu.2025.1538516. eCollection 2025.
Most trauma patients require intensive care treatment and are susceptible to developing persistent inflammation and immunosuppression, potentially leading to multi organ dysfunction syndrome (MODS) and dependence on long term care facilities. T cells undergo changes in numbers and function post trauma. T cell dysfunction in polytraumatized patients was characterized using functional immunomonitoring to predict individual clinical outcome. Moreover, the potential to reverse T cell dysfunction using Interleukin (IL)-7 was examined.
Blood samples were drawn from healthy individuals and prospectively enrolled polytrauma patients (Injury Severity Score ≥ 18) on admission, 8, 24 and 48 hours, 5 and 10 days after. CD3/28-stimulated cytokine production of T cells in whole blood was assessed via Enzyme Linked Immuno Spot (ELISpot). T cell subsets were quantified via counting and flow cytometry. Unfavorable physical performative outcome was defined as death or new functional disability necessitating long term care. Secondary outcomes were the development of MODS and in-hospital mortality. IL-7 was added ex vivo to test reversibility of cytokine disturbances.
34 patients were enrolled. The different outcome groups showed no difference in injury severity. Patients with favorable physical performative outcome revealed higher functional T cell specific Interferon γ (IFN-γ) and IL-17 (8 hours) and lower IL-10 production (day 5) and higher CD8 T cell concentrations. Patients without MODS development showed a higher IFN-γ (day 10), higher IL-2 (8 hours) and higher IL-17 production (admission, day 5). There were no differences regarding in-hospital mortality. Systemic blood IFN-γ, IL-2 and IL-10 concentrations only correlated with MODS (24 hours). Systemic CD8 T cell numbers correlated with functional IFN-γ production. Whole blood stimulation with IL-7 increased functional T cell IFN-γ release.
Our study reveals an early characteristic overall T cell dysfunction of pro-inflammatory (IFN-γ, IL-2, IL-17) and immunosuppressive (IL-10) subtypes in polytraumatized patients. Our data indicates that rather the functional capacity of T cells to release cytokines, but not systemic cytokine concentrations can be used to predict outcome post trauma. We assume that the early stimulation of pro- and anti-inflammatory T cells benefits polytraumatized patients. Potentiation of functional IFN-γ release might be achieved by IL-7 administration.
大多数创伤患者需要重症监护治疗，且易发生持续性炎症和免疫抑制，这可能导致多器官功能障碍综合征（MODS）以及对长期护理机构的依赖。创伤后T细胞数量和功能会发生变化。通过功能免疫监测对多发伤患者的T细胞功能障碍进行特征分析，以预测个体临床结局。此外，还研究了使用白细胞介素（IL）-7逆转T细胞功能障碍的可能性。
采集健康个体以及前瞻性纳入的多发伤患者（损伤严重度评分≥18）入院时、入院后8小时、24小时、48小时、5天和10天的血样。通过酶联免疫斑点法（ELISpot）评估全血中经CD3/28刺激的T细胞细胞因子产生情况。通过计数和流式细胞术对T细胞亚群进行定量分析。不良身体表现结局定义为死亡或出现需要长期护理的新功能残疾。次要结局为MODS的发生和院内死亡率。体外添加IL-7以测试细胞因子紊乱的可逆性。
共纳入34例患者。不同结局组在损伤严重程度上无差异。身体表现结局良好的患者显示出更高的功能性T细胞特异性干扰素γ（IFN-γ）和IL-17（8小时），更低的IL-10产生（第5天）以及更高的CD8 T细胞浓度。未发生MODS的患者显示出更高的IFN-γ（第10天）、更高的IL-2（8小时）和更高的IL-17产生（入院时、第5天）。院内死亡率方面无差异。全身血液中的IFN-γ、IL-2和IL-10浓度仅与MODS（24小时）相关。全身CD8 T细胞数量与功能性IFN-γ产生相关。用IL-7对全血进行刺激可增加功能性T细胞IFN-γ释放。
我们的研究揭示了多发伤患者中存在促炎（IFN-γ、IL-2、IL-17）和免疫抑制（IL-10）亚型的早期特征性整体T细胞功能障碍。我们的数据表明，可用于预测创伤后结局的是T细胞释放细胞因子的功能能力，而非全身细胞因子浓度。我们推测，早期刺激促炎和抗炎T细胞对多发伤患者有益。给予IL-7可能实现功能性IFN-γ释放的增强。
