Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UK.
Dig Dis. 2010;28(1):63-9. doi: 10.1159/000282066. Epub 2010 May 7.
The histological lesion of interface hepatitis, with its dense portal cell infiltrate consisting of lymphocytes, monocytes/macrophages and plasma cells, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of autoimmune hepatitis (AIH). Immunohistochemical studies, focused on the phenotype of inflammatory cells infiltrating the liver parenchyma, have shown a predominance of alphabeta-T cells. Amongst these cells, the majority have been CD4 helper/inducers, while a sizeable minority have consisted of CD8 cytotoxic/suppressors. Lymphocytes on non-T cell lineage included natural killer cells, monocytes/macrophages and B lymphocytes. For autoimmunity to arise, the self-antigenic peptide, embraced by an human leukocyte antigen (HLA) class II molecule, must be presented to an uncommitted T helper (T(H)0) lymphocyte by professional antigen-presenting cells. Once activated and according to the presence in the milieu of interleukin 12 (IL-12) or IL-4, T(H)0 lymphocytes can differentiate into T(H)1 cells, which are pivotal to macrophage activation; enhance HLA class I expression, rendering liver cells vulnerable to CD8 T-cell attack; and induce HLA class II expression on hepatocytes; or they can differentiate into T(H)2 cells, which produce IL-4, IL-10 and IL-13, cytokines favouring autoantibody production by B lymphocytes. Autoantigen recognition is tightly controlled by regulatory mechanisms, such as those exerted by CD4+CD25(high) regulatory T cells. Numerical and functional regulatory T cell impairment characterises AIH and permits the perpetuation of effector immune responses with ensuing persistent liver destruction. Advances in the study of autoreactive T cells stem mostly from AIH type 2, where the main autoantigen, cytochrome P450IID6 (CYP2D6), is known to enable characterisation of antigen-specific immune responses.
界面性肝炎的组织学病变，其密集的门管区细胞浸润由淋巴细胞、单核细胞/巨噬细胞和浆细胞组成，首先提示自身免疫性肝炎（AIH）发病机制中的自身免疫性细胞攻击。免疫组织化学研究集中在浸润肝实质的炎症细胞表型上，显示出alphabeta-T 细胞的优势。在这些细胞中，大多数是 CD4 辅助/诱导细胞，而相当一部分是 CD8 细胞毒性/抑制细胞。非 T 细胞谱系的淋巴细胞包括自然杀伤细胞、单核细胞/巨噬细胞和 B 淋巴细胞。为了产生自身免疫，被人类白细胞抗原（HLA）II 类分子所包含的自身抗原肽必须由专业的抗原呈递细胞呈递给未分化的辅助性 T 细胞（T(H)0）。一旦被激活，根据微环境中白细胞介素 12（IL-12）或 IL-4 的存在，T(H)0 淋巴细胞可以分化为 T(H)1 细胞，这对于巨噬细胞的激活至关重要；增强 HLA 类 I 表达，使肝细胞容易受到 CD8 T 细胞的攻击；并诱导肝细胞表达 HLA 类 II；或者它们可以分化为 T(H)2 细胞，产生 IL-4、IL-10 和 IL-13，这些细胞因子有利于 B 淋巴细胞产生自身抗体。自身抗原的识别受到调节机制的严格控制，如 CD4+CD25(high)调节性 T 细胞所发挥的调节机制。数量和功能上的调节性 T 细胞损伤是 AIH 的特征，允许效应免疫反应的持续存在，并随之导致持续的肝破坏。自身反应性 T 细胞研究的进展主要源于 AIH 2 型，其中主要的自身抗原细胞色素 P450IID6（CYP2D6）能够使抗原特异性免疫反应得以特征化。
