Geenen V, Goxe B, Martens H, Vandersmissen E, Vanneste Y, Achour I, Kecha O, Lefebvre P J
Department of Medicine-Endocrinology, University of Liège, Liège-Sart Tilman, Belgium.
J Mol Med (Berl). 1995 Sep;73(9):449-55. doi: 10.1007/BF00202263.
Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental observations which support a dual role in T cell selection played by the thymic repertoire of neuroendocrine polypeptide precursors. Through the mode of cryptocrine intercellular signaling thymic neuroendocrine-related precursors synthesized in thymic epithelial cells have been shown to influence the early steps in T cell differentiation. In addition, thymic neuroendocrine-related polypeptides are a source of self-antigens which are presented by the major histocompatibility system of the thymic epithelium. Preliminary data also suggest that the intrathymic T cell education to neuroendocrine self-antigens is not strictly superimposible to the antigen presentation by dedicated presenting cells. Insulin-like growth factor-II (IGF-II) was identified as one dominant member of the insulin family expressed by thymic epithelial and nurse cells. The intrathymic presentation of IGF-II or IGF-II derived self-antigens is under current investigation. If further confirmed, the central tolerogenic properties of IGF-II could be considered in the elaboration of a strategy for an efficient and safe prevention of insulin-dependent diabetes.
在系统发育和个体发育过程中，胸腺都表现为细胞间信号传导的两个主要系统——神经内分泌系统和免疫系统之间的一个节点。本综述介绍了一些实验观察结果，这些结果支持胸腺中神经内分泌多肽前体库在T细胞选择中发挥双重作用。通过隐分泌细胞间信号传导方式，已证明胸腺上皮细胞中合成的胸腺神经内分泌相关前体可影响T细胞分化的早期步骤。此外，胸腺神经内分泌相关多肽是自身抗原的一个来源，由胸腺上皮的主要组织相容性系统呈递。初步数据还表明，胸腺内针对神经内分泌自身抗原的T细胞教育与专职呈递细胞的抗原呈递并不完全重叠。胰岛素样生长因子-II（IGF-II）被确定为胸腺上皮细胞和哺育细胞表达的胰岛素家族的一个主要成员。目前正在研究IGF-II或IGF-II衍生的自身抗原在胸腺内的呈递情况。如果得到进一步证实，IGF-II的中枢致耐受性特性可在制定有效且安全的胰岛素依赖型糖尿病预防策略时加以考虑。
