Experimental autoimmune encephalomyelitis (EAE) is commonly used as an animal model for evaluating clinical, histological and immunological processes potentially relevant to the human disease multiple sclerosis (MS), for which the mode of disease induction remains largely unknown. An important caveat for interpreting EAE processes in mice is the inflammatory effect of immunization with myelin peptides emulsified in complete Freund’s adjuvant (CFA), often followed by additional injections of pertussis toxin (Ptx) in some strains to induce EAE. The current study evaluated clinical, histological, cellular (spleen), and chemokine-driven processes in spinal cords of male vs. female C57BL/6 mice that were immunized with mouse (m)MOG-35-55/CFA/Ptx to induce EAE; immunized with saline/CFA/Ptx only (CFA, no EAE); or were untreated (Naïve, no EAE). Analysis of response curves utilized a rigorous and sophisticated methodology to parse and characterize the effects of EAE and adjuvant alone vs. the Naive baseline responses. The results demonstrated stronger pro-inflammatory responses of immune cells and their associated cytokines, chemokines, and receptors in male vs. female CFA and EAE mice that appeared to be offset partially by increased percentages of male anti-inflammatory, regulatory and checkpoint T cell, B cell, and monocyte/macrophage subsets. These sex differences in peripheral immune responses may explain the reduced cellular infiltration and differing chemokine profiles in the central nervous system (CNS) of male vs. female CFA immunized mice and the reduced CNS infiltration and demyelination observed in male vs. female EAE groups of mice that ultimately resulted in the same clinical EAE disease severity in both sexes. Our findings suggest EAE disease severity is governed not only by the degree of CNS infiltration and demyelination, but also by the balance of pro-inflammatory vs. regulatory cell types and their secreted cytokines and chemokines.

实验性自身免疫性脑脊髓炎 (EAE) 通常用作评估与人类疾病多发性硬化症 (MS) 潜在相关的临床、组织学和免疫学过程的动物模型，而疾病诱导的模式在很大程度上仍然未知。解释小鼠 EAE 过程的一个重要警告是用完全弗氏佐剂 (CFA) 乳化的髓鞘肽免疫的炎症效应，通常随后在某些菌株中额外注射百日咳毒素 (Ptx) 以诱导 EAE。目前的研究评估了雄性和雌性 C57BL/6 小鼠脊髓中的临床、组织学、细胞（脾脏）和趋化因子驱动过程，这些小鼠用小鼠 (m)MOG-35-55/CFA/Ptx 免疫以诱导 EAE ; 仅用盐水/CFA/Ptx 免疫（CFA，无 EAE）；或未经治疗（天真，无 EAE）。响应曲线的分析使用了严格而复杂的方法来解析和表征单独的 EAE 和佐剂与 Naive 基线响应的效果。结果表明，在雄性 CFA 和 EAE 小鼠中，免疫细胞及其相关细胞因子、趋化因子和受体的促炎反应更强，这似乎被雄性抗炎、调节和检查点 T 细胞百分比增加部分抵消， B 细胞和单核细胞/巨噬细胞亚群。这些外周免疫反应的性别差异可以解释雄性和雌性 CFA 免疫小鼠的中枢神经系统 (CNS) 细胞浸润减少和趋化因子谱不同，以及在雄性和小鼠中观察到的 CNS 浸润和脱髓鞘减少。雌性 EAE 小鼠组最终导致两种性别的临床 EAE 疾病严重程度相同。我们的研究结果表明，EAE 疾病的严重程度不仅取决于 CNS 浸润和脱髓鞘的程度，还取决于促炎细胞与调节细胞类型及其分泌的细胞因子和趋化因子的平衡。