CD4+ Vα14 natural killer T cells are essential for acceptance of rat islet xenografts in mice
CD4+ Vα14 natural killer T cells are essential for acceptance of rat islet xenografts in mice
复制标题
DOI：
10.1172/jci8922
复制
发表时间：
2000-06-01
影响因子：
15.9
通讯作者：
Ikeda, S
中科院分区：
文献类型：
--
作者：
Ikehara, Y;Yasunami, Y;Ikeda, S
胰岛移植是治疗胰岛素依赖型糖尿病的一种潜在方法。然而，针对同种异体和异种移植胰岛的免疫反应的精确细胞和分子机制仍不清楚。在这里，我们证明，CD 4（+）V α 14自然杀伤T（NKT）细胞，最近确定的淋巴样细胞谱系，需要接受肝内大鼠胰岛异种移植。移植后给予抗CD 4单克隆抗体，使胰岛异种移植物被C57 BL/6小鼠接受，而不需要免疫抑制药物。抗-CD 4 mAb的剂量是关键的，并且有益效果似乎与移植后约14天的CD 4（+）NKT细胞的重新出现有关。有趣的是，尽管抗-CD 4 mAb治疗，在V α 14 NKT细胞缺陷小鼠中，大鼠胰岛异种移植物被排斥，所述小鼠显示常规淋巴样细胞的正常补体;将Ver 14 NKT细胞过继转移到Vee 14 NKT细胞缺陷小鼠中恢复了大鼠胰岛异种移植物的接受。此外，大鼠胰岛异种移植物被仅具有Va 14 NKT细胞而没有其它淋巴样细胞的V α 14 NKT小鼠接受。这些结果表明，V α 14 NKT细胞在用抗CD 4抗体处理的小鼠中接受大鼠胰岛异种移植物中起关键作用，可能是作为免疫抑制调节细胞。
Pancreatic islet transplantation represents a potential treatment for insulin-dependent diabetes mellitus. However, the precise cellular and molecular mechanisms of the immune reactions against allogeneic and xenogeneic transplanted islets remain unclear. Here, we demonstrate that CD4(+) V alpha 14 natural killer T (NKT) cells, a recently identified lymphoid cell lineage, are required for the acceptance of intrahepatic rat islet xenografts. An anti-CD4 mAb, administrated after transplantation, allowed islet xenografts to be accepted by C57BL/6 mice, with no need for immunosuppressive drugs. The dose of anti-CD4 mAb was critical, and the beneficial effect appeared to be associated with the reappearance of CD4(+) NKT cells at around 14 days after transplantation Interestingly, rat islet xenografts were rejected, despite the anti-CD4 mAb treatment, in V alpha 14 NKT cell-deficient mice, which exhibit the normal complement of conventional lymphoid cells; adoptive transfer of Ver 14 NKT cells into Vee 14 NKT cell-deficient mice restored the acceptance of rat islet xenografts. In addition, rat islet xenografts were accepted by V alpha 14 NKT mice having only Va14 NKT cells and no other lymphoid cells. These results indicate that V alpha 14 NKT cells play a crucial role in the acceptance of rat islet xenografts in mice treated with anti-CD4 antibody, probably by serving as immunosuppressive regulatory cells.