Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Trends Immunol. 2011 Aug;32(8):345-9. doi: 10.1016/j.it.2011.05.003. Epub 2011 Jun 21.
T cell immunoglobulin-3 (Tim-3) has been identified as a marker of differentiated interferon-γ-producing CD4(+) T helper type 1 and CD8(+) T cytotoxic type 1 cells. The interaction of Tim-3 with its ligand, galectin-9 (Gal-9), induces cell death, and in vivo blockade of this interaction results in exacerbated autoimmunity and abrogation of tolerance in experimental models, establishing Tim-3 as a negative regulatory molecule. Recent studies have uncovered additional mechanisms by which Tim-3 negatively regulates T cell responses, such as promoting the development of CD8(+) T cell exhaustion and inducing expansion of myeloid-derived suppressor cells. In contrast to this inhibitory effect on T cells, Tim-3-Gal-9 interaction promotes macrophage clearance of intracellular pathogens. Here, we focus on the emerging role for Tim-3 in tumor and antimicrobial immunity.
T 细胞免疫球蛋白-3（Tim-3）已被鉴定为分化的干扰素-γ产生的 CD4(+)T 辅助 1 型和 CD8(+)T 细胞毒性 1 型细胞的标志物。Tim-3 与其配体半乳糖凝集素-9（Gal-9）的相互作用诱导细胞死亡，体内阻断这种相互作用会导致自身免疫加重，并在实验模型中消除耐受，从而确立 Tim-3 作为负调控分子。最近的研究揭示了 Tim-3 负调控 T 细胞反应的其他机制，例如促进 CD8(+)T 细胞耗竭的发展和诱导髓系来源的抑制细胞的扩增。与对 T 细胞的这种抑制作用相反，Tim-3-Gal-9 相互作用促进了巨噬细胞清除细胞内病原体。在这里，我们重点介绍 Tim-3 在肿瘤和抗菌免疫中的新作用。
