Masuda K, Makino Y, Cui J, Ito T, Tokuhisa T, Takahama Y, Koseki H, Tsuchida K, Koike T, Moriya H, Amano M, Taniguchi M
Japan Science and Technology Corporation (JST), School of Medicine, Chiba University, Japan.
J Immunol. 1997 Mar 1;158(5):2076-82.
A novel subset of peripheral T cells, peripheral NK T cells, is found to be a major population comprising 5% of splenic T and 40% of bone marrow T cells. The majority of peripheral NK T cells are characterized by the expression of an invariant TCR-alpha encoded by V alpha 14/J alpha 281 with a one nucleotide N region. Moreover, a specific reduction of V alpha 14+ NK T cells has been demonstrated to be tightly associated with various autoimmune diseases, indicating their decisive role in autoimmune disease development. In this study, we investigated the phenotypes of peripheral V alpha 14+ NK T cells and their TCR-beta repertoire. Peripheral V alpha 14+ NK T cells, comprise two populations, i.e., small and large sized cells, at an equal frequency, belonged to the CD4- CD8- fraction, and are heat stable antigen(bright), macrophage-1bright, B220bright, CD45RBdim, and Mel-14dim, but CD5-, distinct from thymic NK T cells. TCR-beta analysis clearly showed that peripheral V alpha 14+ NK T cells utilized two to three dominant invariant TCR-beta, such as V beta 8.2 D beta J beta 2.5/V beta 7 D beta J beta 2.1 in the spleen and liver, V beta 8.2 D beta J beta 2.5/V beta 8.3 D beta J beta 2.2/V beta 7 D beta J beta 2.6 in the bone marrow, and V beta 7 D beta J beta 2.1/V beta 3 D beta J beta 1.2 in intestinal intraepithelial lymphocytes. Judging from the unusual surface phenotypes, such as heat stable antigen, macrophage-1, B220, CD45RBdim, and Mel-14dim, which are known to be T cell activation markers, peripheral V alpha 14+ NK T cells may always be activated under physiologic conditions, resulting in the oligoclonal expansion of V alpha 14+ NK T cells with different invariant TCR-beta in different peripheral organs. The unique features of V alpha 14+ NK T cells are discussed.
一种新型外周T细胞亚群,即外周自然杀伤T细胞(peripheral NK T cells),被发现是一个主要群体,占脾T细胞的5%和骨髓T细胞的40%。大多数外周自然杀伤T细胞的特征是表达由Vα14/Jα281编码的恒定TCR-α,带有一个单核苷酸N区。此外,已证明Vα14+自然杀伤T细胞的特异性减少与各种自身免疫性疾病密切相关,表明它们在自身免疫性疾病发展中起决定性作用。在本研究中,我们调查了外周Vα14+自然杀伤T细胞的表型及其TCR-β库。外周Vα14+自然杀伤T细胞由两个群体组成,即小细胞和大细胞,频率相等,属于CD4-CD8-亚群,热稳定抗原呈明亮表达(bright),巨噬细胞-1呈明亮表达,B220呈明亮表达,CD45RB呈低表达,Mel-14呈低表达,但CD5呈阴性,与胸腺自然杀伤T细胞不同。TCR-β分析清楚地表明,外周Vα14+自然杀伤T细胞利用两到三种主要的恒定TCR-β,如脾脏和肝脏中的Vβ8.2 DβJβ2.5/Vβ7 DβJβ2.1、骨髓中的Vβ8.2 DβJβ2.5/Vβ8.3 DβJβ2.2/Vβ7 DβJβ2.6以及肠道上皮内淋巴细胞中的Vβ7 DβJβ2.1/Vβ3 DβJβ1.2。从热稳定抗原、巨噬细胞-1、B220、CD45RBdim和Mel-14dim等已知为T细胞活化标志物的异常表面表型来看,外周Vα14+自然杀伤T细胞在生理条件下可能总是被激活,导致不同外周器官中具有不同恒定TCR-β的Vα14+自然杀伤T细胞发生寡克隆扩增。本文讨论了Vα14+自然杀伤T细胞的独特特征。