There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined Teff/Treg subsets both before and after ex vivo anti-CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 symptomatic remitted BD patients and 21 healthy controls and assessed human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of unstimulated CD3 + CD8 + CD71+ and CD4 + CD25 + FOXP3 and increased CD4 + CD25 + FOXP3 + CD152+ frequencies and with lowered stimulated frequencies of CD3 + CD8 + CD71+, CD4 + CD25 + FOXP3 + CD152+, and CD4 + CD25 + FOXP3 + GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3 + CD4 + CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4 + CD25 + FOXP+GARP T phenotypes. In conclusion, in BD patients, immune injuries, staging, and HCMV seropositivity interact and cause CIRS dysfunctions and exaggerated IRS responses, which play a key role in parainflammation and neuroaffective toxicity. HCMV seropositivity contributes to an immune-risk phenotype in BD.

中文翻译：

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双相情感障碍中外周血 T 效应细胞和 T 调节淋巴细胞的损伤与疾病分期和抗巨细胞病毒 IgG 水平有关。

现在有证据表明，根据细胞因子谱，双相情感障碍 (BD) 伴随着免疫炎症反应系统 (IRS) 和补偿性免疫调节系统 (CIRS) 的同时激活，并且这两种成分可能与疾病的分期。然而，没有 BD 研究使用由外周血活化 T 效应子 (Teff) 和 T 调节 (Treg) 亚群表达的 CD（分化簇）分子评估 IRS/CIRS 比率。本研究在 25 名症状缓解的 BD 患者和 21 名健康对照中使用流式细胞术免疫表型分析了体外抗 CD3/CD28 刺激前后的 Teff/Treg 亚群，并评估了人巨细胞病毒 (HCMV) 特异性 IgG 抗体。BD 与未受刺激的 CD3 + CD8 + CD71+ 和 CD4 + CD25 + FOXP3 的频率显着降低以及 CD4 + CD25 + FOXP3 + CD152+ 频率的增加以及 CD3 + CD8 + CD71+、CD4 + CD25 + FOXP3 + CD152+ 的受刺激频率降低有关和 CD4 + CD25 + FOXP3 + GARP 细胞，因此，受刺激的 Teff/Treg 比率增加。此外，躁狂发作次数（而非轻躁狂或抑郁发作）与 CD4+ 和 CD8+ 细胞上 CD3 + CD4 + CD154+ 和 CD69+ 和 CD71+ 表达的刺激比例显着负相关，同时疾病持续时间（≥ 10 年）伴随着受刺激的 CD152+ Treg、CD1​​54+ 和 CD71+ CD4+ T 细胞的消耗频率。BD 和抗人巨细胞病毒 (HCMV) IgG 水平显着相互作用以降低 CD4 + CD25 + FOXP + GARP T 表型的表达。总之，在 BD 患者中，免疫损伤、分期和 HCMV 血清阳性相互作用并导致 CI​​RS 功能障碍和夸大的 IRS 反应，这在副炎症和神经毒性毒性中起关键作用。HCMV 血清阳性有助于 BD 中的免疫风险表型。