Mieza M A, Itoh T, Cui J Q, Makino Y, Kawano T, Tsuchida K, Koike T, Shirai T, Yagita H, Matsuzawa A, Koseki H, Taniguchi M
Division of Molecular Immunology, Center for Biomedical Science, School of Medicine, Chiba University, Japan.
J Immunol. 1996 May 15;156(10):4035-40.
A novel peripheral T cell subset characterized by the expression of a NK marker and invariant TCR encoded by V alpha 14 J alpha 281 gene segments with a 1-base N-region was investigated in relation to autoimmune disease development. First, we observed that invariant V alpha 14+ NK T cells are specifically reduced with aging in C57BL/6 lpr/lpr or MRL lpr/lpr mice, whereas no change was observed in age-matched control C57BL/6 or MRL +/+ mice as determined by FACS analysis and RNase protection assay. This reduction precedes the disease development and could also be detected in other autoimmune disease-prone mice, such as C3H gld/gld and (NZB x NZW)F1 mice. These results suggest that the specific decrease in invariant V alpha 14+ NK T cells correlates strongly with the development of autoimmunity. Second, injection of MRL lpr/lpr mice with anti-V alpha 14 mAb resulted in the early onset and exacerbation of lymphosplenomegaly due to the accumulation of abnormal CD3+ B220+ CD4-CD8- T cells as well as an increase in the titers of anti-dsDNA autoantibodies. These results indicate that V alpha 14+ NK T cells regulate autoimmune responses and play a crucial role in controlling the development of autoimmune diseases.
研究了一种新型外周T细胞亚群，其特征是表达一种NK标志物以及由Vα14 Jα281基因片段编码且带有1个碱基N区的恒定TCR，并探讨了其与自身免疫性疾病发展的关系。首先，我们观察到，通过流式细胞术分析和核糖核酸酶保护试验确定，在C57BL/6 lpr/lpr或MRL lpr/lpr小鼠中，恒定Vα14+ NK T细胞会随着年龄增长而特异性减少，而在年龄匹配的对照C57BL/6或MRL +/+小鼠中未观察到变化。这种减少在疾病发展之前就已出现，并且在其他易患自身免疫性疾病的小鼠中也能检测到，如C3H gld/gld和（NZB×NZW）F1小鼠。这些结果表明，恒定Vα14+ NK T细胞的特异性减少与自身免疫性的发展密切相关。其次，给MRL lpr/lpr小鼠注射抗Vα14单克隆抗体，由于异常CD3+B220+CD4 - CD8 - T细胞的积累以及抗双链DNA自身抗体滴度的增加，导致淋巴脾肿大提前出现并加重。这些结果表明，Vα14+ NK T细胞调节自身免疫反应，并在控制自身免疫性疾病的发展中起关键作用。
