Bimodal regulation of T cell-mediated immune responses by TIM-4
Bimodal regulation of T cell-mediated immune responses by TIM-4
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DOI：
10.1093/intimm/dxn029
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发表时间：
2008-05-01
影响因子：
4.4
通讯作者：
Kikutani, Hitoshi
中科院分区：
文献类型：
--
作者：
Mizui, Masayuki;Shikina, Takashi;Kikutani, Hitoshi
T细胞IG和粘蛋白结构域（TIM）-4优先在抗原呈递细胞上表达，并且其反配体TIM-1被认为向T细胞递送共刺激信号。然而，TIM-4的生理功能仍不清楚。在这里，我们证明了TIM-4通过TIM-1以外的配体抑制幼稚T细胞活化。TIM-4的抑制作用对不表达TIM-1的初始T细胞是特异性的，并且该作用在预活化的T细胞中消失。相反，尽管抗原特异性T细胞的产生增加，但抗体介导的TIM-4体内阻断基本上抑制了T细胞介导的炎症反应。此外，用抗TIM-4治疗减少了用抗原致敏的T细胞过继转移的小鼠中产生的炎症反应。这些结果表明，TIM-4发挥双峰功能，这取决于T细胞的活化状态。
T cell Ig and mucin domain (TIM)-4 is preferentially expressed on antigen-presenting cells, and its counter-ligand, TIM-1, is thought to deliver co-stimulating signals to T cells. However, the physiological functions of TIM-4 remain unclear. Here, we demonstrate that TIM-4 inhibits naive T cell activation through a ligand other than TIM-1. The inhibitory effect of TIM-4 was specific to naive T cells which do not express TIM-1, and the effect disappeared in pre-activated T cells. Conversely, antibody-mediated blockade of TIM-4 in vivo substantially suppressed T cell-mediated inflammatory responses despite enhanced generation of antigen-specific T cells. Furthermore, treatment with anti-TIM-4 reduced the inflammatory responses developed in mice that were adoptively transferred with antigen-primed T cells. These results suggest that TIM-4 exerts bimodal functions depending on the activation status of T cells.