Key inhibitory proteins can blunt immune responses to self-antigens, and deficiencies in this repertoire may promote autoimmunity. The goals of this review are to describe the key immune inhibitory proteins, indicate their possible impact on the development of autoimmune disease, especially autoimmune hepatitis, and encourage studies to clarify their pathogenic role and candidacy as therapeutic targets. English abstracts were identified in PubMed by multiple search terms. Full length articles were selected for review, and secondary and tertiary bibliographies were developed. Cytotoxic T lymphocyte antigen-4 impairs ligation of CD28 to B7 ligands on antigen presenting cells and inhibits the adaptive immune response by increasing anti-inflammatory cytokines, generating regulatory T cells, and reducing T cell activation and proliferation. Programed cell death antigen-1 inhibits T cell selection, activation, and proliferation by binding with two ligands at different phases and locations of the immune response. A soluble alternatively spliced variant of this protein can dampen the inhibitory signal. Autoimmune hepatitis has been associated with polymorphisms of the cytotoxic T lymphocyte antigen-4 gene, reduced hepatic expression of a ligand of programed cell death antigen-1, an interfering soluble variant of this key inhibitory protein, and antibodies against it. Findings have been associated with laboratory indices of liver injury and suboptimal treatment response. Abatacept, belatacept, CD28 blockade, and induction of T cell exhaustion are management considerations that require scrutiny. In conclusion, deficiencies in key immune inhibitory proteins may promote the occurrence of autoimmune diseases, such as autoimmune hepatitis, and emerging interventions may overcome these deficiencies. Investigations should define the nature, impact and management of these inhibitory disturbances in autoimmune hepatitis.

中文翻译：

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免疫抑制蛋白及其在自身免疫性和自身免疫性肝炎中的致病性和治疗意义。

关键的抑制蛋白可以钝化对自身抗原的免疫反应，而该库中的缺陷可能会促进自身免疫。这篇综述的目的是描述关键的免疫抑制蛋白，表明它们对自身免疫性疾病，尤其是自身免疫性肝炎的发展可能产生的影响，并鼓励进行研究以阐明其作为治疗靶点的致病作用和候选资格。在PubMed中通过多个搜索词识别了英文摘要。选择完整的文章进行审查，并开发了二级和三级参考书目。细胞毒性T淋巴细胞抗原4会破坏CD28与抗原呈递细胞上的B7配体的连接，并通过增加抗炎细胞因子，产生调节性T细胞并减少T细胞的活化和增殖来抑制适应性免疫反应。程序性细胞死亡抗原-1通过在免疫反应的不同阶段和位置与两个配体结合，抑制T细胞的选择，活化和增殖。该蛋白的可溶性或可变剪接变体可以减弱抑制信号。自身免疫性肝炎与细胞毒性T淋巴细胞抗原4基因的多态性，程序性细胞死亡抗原1的配体的肝表达降低，该关键抑制蛋白的干扰性可溶变异体及其抗体有关。研究结果与肝脏损伤的实验室指标和治疗效果欠佳相关。Abatacept，belatacept，CD28阻滞和诱导T细胞衰竭是需要仔细研究的管理考虑因素。结论，关键免疫抑制蛋白的缺陷可能会促进自身免疫性疾病（例如自身免疫性肝炎）的发生，而新兴的干预措施可能会克服这些缺陷。研究应确定自身免疫性肝炎中这些抑制性疾病的性质，影响和处理。