Abo T, Watanabe H, Sato K, Iiai T, Moroda T, Takeda K, Seki S
Department of Immunology, Niigata University School of Medicine, Japan.
Nat Immun. 1995 Apr;14(4):173-87.
A series of recent studies have revealed that extrathymic pathways of T cell differentiation exist at multiple sites in mice and humans. In terms of their properties, extrathymic T cells may stand at an intermediate position between natural killer (NK) cells and thymus-derived T cells in phylogenetic development. It is speculated that primitive lymphocytes such as NK cells and extrathymic T cells develop from primordial macrophages in intraepithelial regions of e.g., the intestine, skin and liver. In this regard, the immune system of the bone marrow and thymus is relatively recent, developing after the emergence of living beings onto the land (i.e., amphibia). A complete elimination of self-reactive T cell clones occurs in mainstream intrathymic T cell differentiation and a consistent generation of such clones occurs through the extrathymic pathways. Therefore, thymus-derived T cells are efficient for processing foreign antigens, whereas extrathymic T cells recognize abnormal self-cells. Although thymus-derived T cells play the major role in youth, extrathymic T cells may play rather a pivotal role with aging and under conditions of malignancy, intracellular infections, pregnancy, and autoimmune diseases.
最近一系列研究表明，在小鼠和人类的多个部位存在T细胞分化的胸腺外途径。就其特性而言，胸腺外T细胞在系统发育过程中可能处于自然杀伤（NK）细胞和胸腺来源的T细胞之间的中间位置。据推测，诸如NK细胞和胸腺外T细胞等原始淋巴细胞是从例如肠道、皮肤和肝脏的上皮内区域的原始巨噬细胞发育而来的。在这方面，骨髓和胸腺的免疫系统相对较新，是在生物登陆（即两栖动物）之后发展起来的。在主流的胸腺内T细胞分化过程中会完全消除自身反应性T细胞克隆，而通过胸腺外途径则会持续产生此类克隆。因此，胸腺来源的T细胞在处理外来抗原方面效率很高，而胸腺外T细胞则识别异常的自身细胞。尽管胸腺来源的T细胞在年轻时起主要作用，但胸腺外T细胞在衰老以及恶性肿瘤、细胞内感染、妊娠和自身免疫性疾病等情况下可能发挥关键作用。
