Division of Immunology, Children's Hospital Boston, Boston, MA 02115, USA.
J Immunol. 2010 Dec 1;185(11):6839-49. doi: 10.4049/jimmunol.1001360. Epub 2010 Oct 29.
Adaptive immunity is characterized by the expansion of an Ag-specific T cell population following Ag exposure. The precise mechanisms, however, that control the expansion and subsequent contraction in the number of Ag-specific T cells are not fully understood. We show that T cell/transmembrane, Ig, and mucin (TIM)-4, a receptor for phosphatidylserine, a marker of apoptotic cells, regulates adaptive immunity in part by mediating the removal of Ag-specific T cells during the contraction phase of the response. During Ag immunization or during infection with influenza A virus, blockade of TIM-4 on APCs increased the expansion of Ag-specific T cells, resulting in an increase in secondary immune responses. Conversely, overexpression of TIM-4 on APCs in transgenic mice reduced the number of Ag-specific T cells that remained after immunization, resulting in reduced secondary T cell responses. There was no change in the total number of cell divisions that T cells completed, no change in the per cell proliferative capacity of the remaining Ag-specific T cells, and no increase in the development of Ag-specific regulatory T cells in TIM-4 transgenic mice. Thus, TIM-4-expressing cells regulate adaptive immunity by mediating the removal of phosphatidylserine-expressing apoptotic, Ag-specific T cells, thereby controlling the number of Ag-specific T cells that remain after the clearance of Ag or infection.
适应性免疫的特点是在抗原暴露后 Ag 特异性 T 细胞群体的扩增。然而，控制 Ag 特异性 T 细胞扩增和随后收缩的确切机制尚未完全了解。我们表明，T 细胞/跨膜、Ig 和粘蛋白（TIM）-4，即凋亡细胞标志物磷脂酰丝氨酸的受体，通过介导反应收缩阶段中 Ag 特异性 T 细胞的清除，部分调节适应性免疫。在 Ag 免疫或感染甲型流感病毒期间，阻断 APC 上的 TIM-4 会增加 Ag 特异性 T 细胞的扩增，从而增加次级免疫反应。相反，在转基因小鼠中，APC 上 TIM-4 的过表达减少了免疫后剩余的 Ag 特异性 T 细胞的数量，导致次级 T 细胞反应减少。T 细胞完成的总细胞分裂数没有变化，剩余的 Ag 特异性 T 细胞的每个细胞增殖能力没有变化，并且在 TIM-4 转基因小鼠中，Ag 特异性调节性 T 细胞的发育没有增加。因此，表达 TIM-4 的细胞通过介导表达磷脂酰丝氨酸的凋亡 Ag 特异性 T 细胞的清除来调节适应性免疫，从而控制清除 Ag 或感染后剩余的 Ag 特异性 T 细胞数量。
