The role of IL-12 in the pathogenesis of the cell-mediated autoimmune diseases
The role of IL-12 in the pathogenesis of the cell-mediated autoimmune diseases
复制标题
DOI：
10.1111/j.1749-6632.1996.tb52670.x
复制
发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Trembleau, S
中科院分区：
文献类型：
--
作者：
Adorini, L;Gregori, S;Trembleau, S
自从最初描述小鼠中分化的CD 4 + T细胞的两个亚群Th 1和Th 2以来，已经过去了十年。对过敏患者T细胞克隆的进一步分析也清楚地定义了人类中抗原特异性Th 1和Th 2细胞。Th 1/Th 2模式迅速成为免疫调节中的关键概念。甚至比其他免疫学二分法更重要的是，将T细胞严格划分为Thl和Th 2显然是过度简化：免疫系统中的调节和效应机制不能被简化为Thl和Th 2细胞。然而，已经清楚地记录了T细胞应答极化为Thl或Th 2表型，特别是在感染和过敏性病症中。感染性疾病代表了Thl和Th 2细胞相关性的最有说服力的例子，因为响应于病原体而发展的T细胞亚群的宿主选择通常是在生与死之间的选择4最近，T细胞细分为Thl和Th 2亚群已经扩展到表明Thl细胞有助于几种T细胞介导的器官特异性自身免疫疾病的发病机制，而Th 2细胞可以抑制疾病的发展。不同的实验模型，如实验性过敏性脑脊髓炎，胰岛素依赖性糖尿病，胶原蛋白11型诱导的关节炎和炎症性肠病，提供了对这种在自身免疫性疾病的调节二分法的支持。这些模型的结果都一致证实了Th 1细胞的致病作用，但Th 2细胞的潜在保护作用仍不清楚。考虑到Th 1和Th 2细胞在调节总抗体产生和控制抗体同种型中的操纵影响，预测Th 1和Th 2细胞在抗体介导的自身免疫性疾病如重症肌无力或系统性红斑狼疮中也起重要作用。
Ten years have now passed since the original description of two subsets of differentiated CD4'T cells in the mouse, Thl and Th2, was first published.'Further analysis of T-cell clones from allergic patients also clearly defined antigen-specific Thl and Th2 cells in humans.* Dispelling do~ bts,~ the Thl/Th2 paradigm rapidly became the key concept in immunoregulation. Even more than other immunological dichotomies, a strict compartmentalization of T cells into Thl and Th2 is obviously an oversimplification: regulatory and effector mechanisms in the immune system cannot be reduced to Thl and Th2 cells. However, the polarization of T-cell responses into the Thl or Th2 phenotype has been clearly documented, notably in infections and in allergic conditions. Infectious diseases represent the most cogent example of the relevance of Thl and Th2 cells, as the host choice of the T-cell subset to be developed in response to the pathogen is often a choice between life and deathe4 Recently, the subdivision of T cells into Thl and Th2 subsets has been extended to suggest that Thl cells contribute to the pathogenesis of several T-cell-mediated organ-specific autoimmune diseases, whereas Th2 cells may inhibit disease development. Support for this dichotomy in the regulation of autoimmune diseases is provided by different experimental models, such as experimental allergic encephalomyelitis, insulin-dependent diabetes mellitus, collagen type 11-induced arthritis and inflammatory bowel disease. Results in these models are all concordant in confirming the pathogenetic role of Thl cells, but the potentially protective role of Th2 cells is still unclear. Considering the steering influence of Thl and Th2 cells in the regulation of total antibody production and in the control of antibody isotypes, Thl and Th2 cells are predicted also to play an important role in antibodymediated autoimmune diseases, such as myasthenia gravis or systemic lupus erythematosus.