Regulation of T cell responses by the receptor molecule Tim-3.
Tim-3 is a member of the T cell immunoglobulin and mucin domain (Tim) family of proteins, which are expressed by several cell types in the immune system, including CD4 and CD8 T cells activated under certain conditions. These molecules are generally thought to act as receptors for multiple ligands and thus to function by engaging intracellular signaling pathways in a ligand-dependent manner. In recent years, the function of the Tim-3 protein has been studied in some detail, particularly with respect to its role in the regulation of CD4 and CD8 T cell responses. Here, we review the structural features of Tim-3, known ligands for this molecule and the links established between Tim-3 and signal transduction pathways. In addition, we review the current literature regarding the role of Tim-3 in the regulation of effector responses by CD4 and CD8 T cells. Overall, findings published thus far strongly support the conclusion that Tim-3 functions to inhibit T cell responses, particularly under conditions involving chronic stimulation. Conversely, some reports have provided evidence that Tim-3 can stimulate T cells under conditions involving acute stimulation, suggesting that the role of Tim-3 may vary depending on context. Further study of Tim-3 is likely to advance our understanding of how CD4 and CD8 T cell responses are regulated and could uncover novel approaches for manipulating T cell function for therapeutic benefit.
Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, 375 Newton Road, 3270 CBRB, Iowa City, IA, 52242, USA.
Jacob V
JV
Gorman
John D
JD
Colgan
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D011173:Portraits as Topic; D015398:Signal Transduction / Q000276:immunology*
C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins