Iiai T, Watanabe H, Seki S, Sugiura K, Hirokawa K, Utsuyama M, Takahashi-Iwanaga H, Iwanaga T, Ohteki T, Abo T
Department of Immunology, Niigata University School of Medicine, Japan.
Immunology. 1992 Dec;77(4):556-63.
We previously demonstrated that the liver may be a major site of extrathymic T-cell differentiation in mice. In the present study, the ontogeny and subsequent development of such T cells in the liver and other organs were investigated. This study was possible because these T cells have T-cell receptors (TcR) of intermediate intensity (i.e. intermediate TcR cells) and constitutively express a high level of interleukin-2 receptor beta chain (IL-2R beta). Therefore the two-colour staining for CD3 (or alpha beta TcR) and IL-2R beta identifies even a small proportion of intermediate TcR cells. The total numbers of mononuclear cells obtained from the liver, thymus and spleen varied from foetal to adult life. Especially in the liver, many haematopoietic cells were present in the parenchymal space at the foetal stage. There were no lymphocytes in the sinusoidal lumen at this period. In contrast, lymphocytes appeared in the hepatic sinusoids after birth and increased with ageing. Phenotypic analysis revealed that intermediate TcR cells appeared in the liver and spleen on Day 4 after birth. Bright TcR cells of thymic origin were also present in the peripheral organs on Day 4. Thereafter, intermediate TcR cells increased in the liver, whereas bright TcR cells increased in the periphery as a function of age. Similarly, thymectomized and congenitally athymic mice had mainly intermediate TcR cells in the liver and, to some extent, periphery. It is concluded that intermediate TcR cells, possibly of extrathymic origin, are generated only after birth and expand with ageing.
我们先前已证明，肝脏可能是小鼠胸腺外T细胞分化的主要场所。在本研究中，对这些T细胞在肝脏及其他器官中的个体发生及后续发育进行了研究。这项研究得以开展是因为这些T细胞具有中等强度的T细胞受体（即中等TcR细胞），并组成性地高水平表达白细胞介素-2受体β链（IL-2Rβ）。因此，对CD3（或αβTcR）和IL-2Rβ进行双色染色，即使是一小部分中等TcR细胞也能被识别出来。从胎儿期到成年期，从肝脏、胸腺和脾脏获取的单核细胞总数各不相同。特别是在肝脏中，胎儿期实质间隙中有许多造血细胞。此时窦状隙腔内没有淋巴细胞。相反，出生后淋巴细胞出现在肝窦中，并随年龄增长而增加。表型分析显示，出生后第4天肝脏和脾脏中出现了中等TcR细胞。出生后第4天，外周器官中也存在胸腺来源的明亮TcR细胞。此后，肝脏中的中等TcR细胞增多，而外周的明亮TcR细胞随年龄增长而增多。同样，胸腺切除的小鼠和先天性无胸腺小鼠肝脏中主要是中等TcR细胞，外周也有一定程度的中等TcR细胞。结论是，中等TcR细胞可能起源于胸腺外，仅在出生后产生，并随年龄增长而扩增。
