Schmoeckel Katrin, Mrochen Daniel M, Hühn Jochen, Pötschke Christian, Bröker Barbara M
Department of Immunology, Institute of Immunology and Transfusion Medicine, University Medicine, Greifswald, Germany.
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
PLoS One. 2018 Feb 7;13(2):e0192197. doi: 10.1371/journal.pone.0192197. eCollection 2018.
Sepsis is frequently complicated by a state of profound immunosuppression, in its extreme form known as immunoparalysis. We have studied the role of the adaptive immune system in the murine acute peritonitis model. To read out adaptive immunosuppression, we primed post-septic and control animals by immunization with the model antigen TNP-ovalbumin in alum, and measured the specific antibody-responses via ELISA and ELISpot assay as well as T-cell responses in a proliferation assay after restimulation. Specific antibody titers, antibody affinity and plasma cell counts in the bone marrow were reduced in post-septic animals. The antigen-induced splenic proliferation was also impaired. The adaptive immunosuppression was positively correlated with an overwhelming general antibody response to the septic insult. Remarkably, antigen "overload" by non-specific immunization induced a similar degree of adaptive immunosuppression in the absence of sepsis. In both settings, depletion of regulatory T cells before priming reversed some parameters of the immunosuppression. In conclusion, our data show that adaptive immunosuppression occurs independent of profound systemic inflammation and life-threatening illness.
脓毒症常并发严重免疫抑制状态，其极端形式称为免疫麻痹。我们在小鼠急性腹膜炎模型中研究了适应性免疫系统的作用。为检测适应性免疫抑制，我们用明矾佐剂中的模型抗原三硝基苯卵清蛋白免疫脓毒症后动物和对照动物作为致敏，通过酶联免疫吸附测定（ELISA）和酶联免疫斑点测定（ELISpot）检测特异性抗体反应，并在再次刺激后的增殖试验中检测T细胞反应。脓毒症后动物的特异性抗体滴度、抗体亲和力和骨髓中的浆细胞计数降低。抗原诱导的脾脏增殖也受损。适应性免疫抑制与对脓毒症刺激的压倒性全身抗体反应呈正相关。值得注意的是，在无脓毒症的情况下，非特异性免疫引起的抗原“过载”诱导了相似程度的适应性免疫抑制。在这两种情况下，致敏前清除调节性T细胞可逆转免疫抑制的一些参数。总之，我们的数据表明，适应性免疫抑制的发生与严重的全身炎症和危及生命的疾病无关。
