Description: The Tim-3-Fc is a soluble fusion protein derived from expression of a fusion of cDNA encoding the entire extracellular domain of mouse Tim-3 to a cDNA encoding a human IgG1 Fc tail. Tim-3 (T cell immunoglobulin- and mucin domain-containing molecule 3) is a type I membrane protein of 281 amino acids whose extracellular domain consists of an immunoglobulin V-like domain followed by a mucin-like region. A secreted form of Tim-3 containing only the immunoglobulin variable domain of the full length molecule has also been identified. Tim-3 is a Th1-specific cell surface molecule. Tim-3 is polymorphic and, as with other Tim family members, it is linked to asthma. Tim-3-Ig fusion proteins, in which Tim-3 was fused to an Fc tail, have been used in vitro and in vivo to study development of Th1 responses. Based on flow cytometric analysis using full-length and soluble mouse Tim-3 fusion proteins, it has been reported that a putative ligand for Tim-3 is expressed on resting CD4-positive T cells, but not on CD8-positive T cells, B cells, or CD11b-positive leukocytes. Some expression was detected on splenic CD11c-positive dendritic cells. Expression of the ligand was downregulated on activated CD4-positive/CD25-negative effector T cells but persisted on CD4-positive/CD25-positive regulatory T cells. Administration of Tim-3-Ig to immunized mice has been reported to cause hyperproliferation of Th1 cells and amplified Th1 cytokine release, as well as abrogation of tolerance induction in Th1 cells. Interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector Th1 cells during a normal immune response and may be crucial for induction of peripheral tolerance.
