Encyclopedia of AIDS

Living Edition
| Editors: Thomas J. Hope, Douglas Richman, Mario Stevenson

Tim-3

Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9610-6_210-1

Definition

T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is a member of the T cell/transmembrane, immunoglobulin, and mucin (TIM) gene family of phosphatidylserine-binding proteins (Freeman et al. 2010). It is a type I transmembrane glycoprotein consisting of an N-terminal IgV-like domain and a heavily glycosylated mucin domain, a transmembrane region, and a cytoplasmic tail. Tim-3 plays a role in the regulation of both innate and adaptive immune responses during autoimmunity, cancer, and chronic infections (Han et al. 2013; Zhu et al. 2011). While it has been shown to both negatively and positively regulate innate immune responses, Tim-3 plays a distinct negative regulatory role in regards to T cell responses. During human immunodeficiency virus type 1 (HIV) infection, Tim-3 marks dysfunctional T cells during chronic stages of infection and acts to dampen responses to viral antigen, contributing to the “exhausted” state of the immune system and lack of viral...

Keywords

Human Immunodeficiency Virus Natural Killer Cell Human Immunodeficiency Virus Infection Adaptive Immune Cell Cell Exhaustion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Fujioka Y, Ohba Y, Gorman JV, Colgan JD, et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012;13:832–42.PubMedCentralPubMedCrossRefGoogle Scholar
  2. Clayton KL, Haaland MS, Douglas-Vail MB, Mujib S, Chew GM, Ndhlovu LC, Ostrowski MA. T cell Ig and mucin domain-containing protein 3 is recruited to the immune synapse, disrupts stable synapse formation, and associates with receptor phosphatases. J Immunol. 2014;192:782–91.PubMedCrossRefGoogle Scholar
  3. Ferris RL, Lu B, Kane LP. Too much of a good thing? Tim-3 and TCR signaling in T cell exhaustion. J Immunol. 2014;193:1525–30.PubMedCrossRefGoogle Scholar
  4. Freeman GJ, Casasnovas JM, Umetsu DT, DeKruyff RH. TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunol Rev. 2010;235:172–89.PubMedCentralPubMedGoogle Scholar
  5. Han G, Chen G, Shen B, Li Y. Tim-3: an activation marker and activation limiter of innate immune cells. Front Immunol. 2013;4:449.PubMedCentralPubMedCrossRefGoogle Scholar
  6. Jones RB, Ndhlovu LC, Barbour JD, Sheth PM, Jha AR, Long BR, Wong JC, Satkunarajah M, Schweneker M, Chapman JM, et al. Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection. J Exp Med. 2008;205:2763–79.PubMedCentralPubMedCrossRefGoogle Scholar
  7. Khaitan A, Unutmaz D. Revisiting immune exhaustion during HIV infection. Curr HIV/AIDS Rep. 2011;8:4–11.PubMedCentralPubMedCrossRefGoogle Scholar
  8. Larsson M, Shankar EM, Che KF, Saeidi A, Ellegard R, Barathan M, Velu V, Kamarulzaman A. Molecular signatures of T-cell inhibition in HIV-1 infection. Retrovirology. 2013;10:31.PubMedCentralPubMedCrossRefGoogle Scholar
  9. Maurya N, Gujar R, Gupta M, Yadav V, Verma S, Sen P. Immunoregulation of dendritic cells by the receptor T cell Ig and mucin protein-3 via Bruton’s tyrosine kinase and c-Src. J Immunol. 2014;193:3417–25.PubMedCrossRefGoogle Scholar
  10. Mujib S, Jones RB, Lo C, Aidarus N, Clayton K, Sakhdari A, Benko E, Kovacs C, Ostrowski MA. Antigen-independent induction of Tim-3 expression on human T cells by the common gamma-chain cytokines IL-2, IL-7, IL-15, and IL-21 is associated with proliferation and is dependent on the phosphoinositide 3-kinase pathway. J Immunol. 2012;188:3745–56.PubMedCrossRefGoogle Scholar
  11. Nakayama M, Akiba H, Takeda K, Kojima Y, Hashiguchi M, Azuma M, Yagita H, Okumura K. Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation. Blood. 2009;113:3821–30.PubMedCrossRefGoogle Scholar
  12. Rangachari M, Zhu C, Sakuishi K, Xiao S, Karman J, Chen A, Angin M, Wakeham A, Greenfield EA, Sobel RA, et al. Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell death and exhaustion. Nat Med. 2012;18:1394–1400.Google Scholar
  13. Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol. 2003;77:4911–27.PubMedCentralPubMedCrossRefGoogle Scholar
  14. Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6:1245–52.PubMedCrossRefGoogle Scholar
  15. Zhu C, Anderson AC, Kuchroo VK. TIM-3 and its regulatory role in immune responses. Curr Top Microbiol Immunol. 2011;350:1–15.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of ImmunologyUniversity of TorontoTorontoCanada
  2. 2.Department of MedicineUniversity of TorontoTorontoCanada
  3. 3.Keenan Research Centre for Biomedical Science of St. Michael’s HospitalTorontoCanada