Tim-3: A co-receptor with diverse roles in T cell exhaustion and tolerance

• Published in: Seminars in immunology Vol. 42; p. 101302
• Main Authors: Tang, Ruihan, Rangachari, Manu, Kuchroo, Vijay K.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-04-2019
• Subjects: Animals; Autoimmunity; Cancer; Coreceptor; Experimental autoimmune encephalomyelitis; Hepatitis A Virus Cellular Receptor 2 - chemistry; Hepatitis A Virus Cellular Receptor 2 - immunology; HIV-1; Humans; Immune checkpoint; Immune Tolerance; Infections - immunology; Inflammation; Ligands; Neoplasms - immunology; Protein Conformation; T cell; T cell exhaustion; T-Lymphocytes - immunology; Tim-3; Autoimmunity; HIV-1; Immune checkpoint; T cell; Experimental autoimmune encephalomyelitis; T cell exhaustion; Inflammation; Coreceptor; Tim-3; Cancer
• ISSN: 1044-5323; 1096-3618
• 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.