Selective reduction of V α 14+ NK T cells associated with disease development in autoimmune-prone mice

作者：Marco Antonio Mieza, Toshiyuki Itoh, J. Cui, Yuko Makino, Tetsu Kawano, Kenichi Tsuchida, Takayoshi Koike, Tsuyoshi Shirai, H Yagita, Akio Matsuzawa, Haruhiko Koseki, Mitsutaka Taniguchi · 发表于：The Journal of Immunology · 年份：1996 · DOI：10.4049/jimmunol.156.10.4035 · 被引用次数：288 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Monoclonal and Polyclonal Antibodies Research

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.