Haynes B F, Hale L P
Department of Medicine, Duke University School of Medicine, Duke Medical Center, Durham, NC, USA.
Immunol Res. 1998;18(2):61-78. doi: 10.1007/BF02788750.
The human thymus is a lymphoepithelial organ in which T cells develop during fetal life. After maturation and selection in the fetal thymic microenvironment, T cells emigrate to peripheral lymphoid tissues such as the spleen, gut, and lymph nodes, and establish the peripheral T cell repertoire. Although the thymus has enormous regenerative capacity during fetal development, the regenerative capacity of the human postnatal thymus decreases over time. With the advent of intensive chemotherapy regimens for a variety of cancer syndromes, and the discovery that infection with the Human Immunodeficiency Virus (HIV) leads to severe loss of CD4+ T cells, has come the need to understand the role of the human thymus in reconstitution of the immune system in adults. During a recent study of the thymus in HIV infection, we observed many CD8+ T cells in AIDS thymuses that had markers consistent with those of mature effector cytotoxic T cells usually found in peripheral immune tissues, and noted these CD8+ effector T cells were predominately located in a thymic zone termed the thymic perivascular space. This article reviews our own work on the thymus in HIV-1 infection, and discusses the work of others that, taken together, suggest that the thymus contains peripheral immune cell components not only in the setting of HIV infection, but also in myasthenia gravis, as well as throughout normal life during the process of thymus involution. Thus, the human thymus can be thought of as a chimeric organ comprised of both central and peripheral lymphoid tissues. These observations have led us to postulate that the thymic epithelial atrophy and decrease in thymopoiesis that occurs in myasthenia gravis, HIV-1 infection, and thymic involution may in part derive from cytokines or other factors produced by peripheral immune cells within the thymic perivascular space.
人类胸腺是一种淋巴上皮器官，T细胞在胎儿期于此发育。在胎儿胸腺微环境中成熟并经过选择后，T细胞迁移至外周淋巴组织，如脾脏、肠道和淋巴结，并建立外周T细胞库。尽管胸腺在胎儿发育过程中具有巨大的再生能力，但人类出生后胸腺的再生能力会随时间下降。随着针对多种癌症综合征的强化化疗方案的出现，以及发现人类免疫缺陷病毒（HIV）感染会导致CD4+T细胞严重缺失，人们开始需要了解人类胸腺在成人免疫系统重建中的作用。在最近一项关于HIV感染中胸腺的研究中，我们在艾滋病患者的胸腺中观察到许多CD8+T细胞，其标志物与通常在外周免疫组织中发现的成熟效应细胞毒性T细胞的标志物一致，并注意到这些CD8+效应T细胞主要位于一个称为胸腺血管周围间隙的胸腺区域。本文回顾了我们自己关于HIV-1感染中胸腺的研究工作，并讨论了其他研究成果，这些研究综合起来表明，胸腺不仅在HIV感染的情况下，而且在重症肌无力中，以及在胸腺退化过程中的整个正常生命过程中，都含有外周免疫细胞成分。因此，人类胸腺可被视为一个由中央和外周淋巴组织组成的嵌合器官。这些观察结果使我们推测，重症肌无力、HIV-1感染和胸腺退化中发生的胸腺上皮萎缩和胸腺生成减少，可能部分源于胸腺血管周围间隙内外周免疫细胞产生的细胞因子或其他因素。
