Arnold Bernd
Molecular Immunology, Deutsches Krebsforschungszentrum DKFZ, Heidelberg, Germany.
Transpl Immunol. 2002 Aug;10(2-3):109-14. doi: 10.1016/s0966-3274(02)00056-4.
The immune system is an adaptive defense system capable of specifically recognizing and eliminating an apparently limitless variety of foreign invaders. This highly specific response is provided by T and B lymphocytes. The enormous diversity of the antigen-specific receptors on these cells is generated by random rearrangement of the respective genes. The key challenge of such a defense system is to have as broad a T and B cell repertoire as possible in the absence of autoreactivity. This review summarizes mechanisms of peripheral T cell tolerance induction seen in various animal models. There is increasing evidence that tolerance to tissue-specific antigens can be induced by dendritic cells in the regional lymph nodes as well as by parenchymal cells like keratinocytes and hepatocytes in the respective tissues. Furthermore, tolerance induction should no longer only be viewed as prevention of T cell activation, as in certain systems activation of autoreactive T cells is insufficient to cause tissue damage. Thus, several tolerance mechanisms are operating in parallel under physiological conditions. With increasing knowledge of the molecular basis we will learn which mechanism is most suitable for therapeutic intervention.
免疫系统是一种适应性防御系统，能够特异性识别并清除种类看似无限的外来入侵者。这种高度特异性的反应由T淋巴细胞和B淋巴细胞提供。这些细胞上抗原特异性受体的巨大多样性是由各自基因的随机重排产生的。这样一种防御系统的关键挑战在于，在不存在自身反应性的情况下，拥有尽可能广泛的T细胞和B细胞库。这篇综述总结了在各种动物模型中所见的外周T细胞耐受诱导机制。越来越多的证据表明，对组织特异性抗原的耐受可由区域淋巴结中的树突状细胞以及相应组织中的实质细胞（如角质形成细胞和肝细胞）诱导产生。此外，耐受诱导不应再仅仅被视为预防T细胞活化，因为在某些系统中，自身反应性T细胞的活化不足以导致组织损伤。因此，在生理条件下，几种耐受机制并行发挥作用。随着对分子基础的了解不断增加，我们将了解哪种机制最适合进行治疗干预。
