Selective reduction of V alpha 14+ NK T cells associated with disease development in autoimmune-prone mice.
Selective reduction of V alpha 14+ NK T cells associated with disease development in autoimmune-prone mice.
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选择性减少 V α 14 NK T 细胞与自身免疫易感小鼠的疾病发展相关。
DOI：
10.4049/jimmunol.156.10.4035
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发表时间：
1996
影响因子：
4.4
通讯作者：
M. Taniguchi
中科院分区：
文献类型：
--
作者：
M. A. Mieza;T. Itoh;J. Cui;Y. Makino;T. Kawano;K. Tsuchida;T. Koike;T. Shirai;H. Yagita;A. Matsuzawa;H. Koseki;M. Taniguchi
研究了一种新的外周T细胞亚群与自身免疫性疾病发展的关系，该亚群的特征在于表达NK标记物和由具有1个碱基N区的V α 14 J α 281基因片段编码的不变TCR。首先，我们观察到不变V α 14+ NK T细胞在C57 BL/6 lpr/lpr或MRL lpr/lpr小鼠中随着年龄的增长而特异性减少，而在年龄匹配的对照C57 BL/6或MRL +/+小鼠中没有观察到变化，如通过FACS分析和RNA酶保护测定所确定的。这种减少在疾病发展之前，并且也可以在其他自身免疫性疾病易感小鼠中检测到，例如C3 H gld/gld和（NZB x NZW）F1小鼠。这些结果表明，特异性的减少，在不变的V α 14+ NK T细胞与自身免疫的发展密切相关。第二，注射抗V α 14 mAb的MRL lpr/lpr小鼠由于异常CD 3 + B220+ CD 4-CD 8- T细胞的积累以及抗dsDNA自身抗体滴度的增加而导致淋巴脾肿大的早期发作和恶化。这些结果表明，V α 14+ 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发挥关键作用。
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.