Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, 60 Fenwood Rd., Boston, MA, 02115, USA.
Department of Neurosciences, Centre de Recherche du CHU de Québec - Université Laval, Pavillon CHUL, 2705 Boul Laurier, Quebec City, QC, G1V 4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Laval University, 1050 Ave de la Médecine, Quebec City, Canada.
Semin Immunol. 2019 Apr;42:101302. doi: 10.1016/j.smim.2019.101302.
T cell inhibitory co-receptors play a crucial role in maintaining the balance between physiologic immune responses and maladaptive ones. T cell immunoglobulin and mucin domain-containing-3 (Tim-3) is a unique inhibitory co-receptor in that its expression is chiefly restricted to interferon (IFN)γ-producing CD4 and CD8 T cells. Early reports firmly established its importance in maintaining peripheral tolerance in transplantation and autoimmunity. However, it has become increasingly clear that Tim-3 expression on T cells, together with other check-point molecules, in chronic infections and cancers can hinder productive immune responses. In this review, we outline what is currently known about the regulation of Tim-3 expression, its ligands and signaling. We discuss both its salutary and deleterious function in immune disorders, as well as the T cell-extrinsic and -intrinsic factors that regulate its function.
T 细胞抑制性共受体在维持生理免疫反应和适应不良免疫反应之间的平衡中起着至关重要的作用。T 细胞免疫球蛋白和粘蛋白结构域包含蛋白 3（Tim-3）是一种独特的抑制性共受体，其表达主要局限于产生干扰素（IFN）γ的 CD4 和 CD8 T 细胞。早期的报告明确了其在移植和自身免疫中维持外周耐受的重要性。然而，越来越明显的是，T 细胞上的 Tim-3 表达与慢性感染和癌症中的其他检查点分子一起，可以阻碍有效的免疫反应。在这篇综述中，我们概述了目前已知的 Tim-3 表达的调节、其配体和信号转导。我们讨论了它在免疫紊乱中的有益和有害功能，以及调节其功能的 T 细胞外在和内在因素。
