Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion

Proceedings of the National Academy of Sciences of the United States of America
Lyndsay AveryLawrence P Kane

Abstract

Tim-3 is highly expressed on a subset of T cells during T cell exhaustion in settings of chronic viral infection and tumors. Using lymphocytic choriomeningitis virus (LCMV) Clone 13, a model for chronic infection, we found that Tim-3 was neither necessary nor sufficient for the development of T cell exhaustion. Nonetheless, expression of Tim-3 was sufficient to drive resistance to PD-L1 blockade therapy during chronic infection. Strikingly, expression of Tim-3 promoted the development of short-lived effector T cells, at the expense of memory precursor development, after acute LCMV infection. These effects were accompanied by increased Akt/mTOR signaling in T cells expressing endogenous or ectopic Tim-3. Conversely, Akt/mTOR signaling was reduced in effector T cells from Tim-3-deficient mice. Thus, Tim-3 is essential for optimal effector T cell responses, and may also contribute to exhaustion by restricting the development of long-lived memory T cells. Taken together, our results suggest that Tim-3 is actually more similar to costimulatory receptors that are up-regulated after T cell activation than to a dominant inhibitory protein like PD-1. These findings have significant implications for the development of anti-Tim-3 antibodi...Continue Reading

References

Dec 22, 1998·The Journal of Experimental Medicine·A J ZajacR Ahmed
May 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Annemieke Th den BoerRené E M Toes
Oct 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·E John WherryRafi Ahmed
Nov 16, 2005·Nature Immunology·Chen ZhuVijay K Kuchroo
Jul 11, 2007·Blood·Susumu NakaeStephen J Galli
Oct 9, 2007·Journal of Virological Methods·Megan M McCausland, Shane Crotty
Jun 23, 2009·Nature·Koichi ArakiRafi Ahmed
Jul 27, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Afework KassuBrent E Palmer
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hyun-Tak JinRafi Ahmed
Sep 8, 2010·The Journal of Experimental Medicine·Kaori SakuishiAna C Anderson
Sep 9, 2010·Proceedings of the National Academy of Sciences of the United States of America·Timothy W HandSusan M Kaech
Jul 9, 2011·Nature Immunology·E John Wherry
Aug 3, 2011·Molecular and Cellular Biology·Judong LeeLawrence P Kane
Oct 20, 2012·Nature Reviews. Immunology·Susan M Kaech, Weiguo Cui
Dec 18, 2013·Frontiers in Immunology·Gencheng HanYan Li
Feb 26, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jacob V GormanJohn D Colgan
May 16, 2014·Immunologic Research·Jacob V Gorman, John D Colgan
Aug 3, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert L FerrisLawrence P Kane
Mar 24, 2015·Trends in Immunology·Kristen E Pauken, E John Wherry
Nov 26, 2015·The Journal of Experimental Medicine·Binh L PhongLawrence P Kane
Mar 17, 2017·International Journal of Molecular Sciences·Wenwen DuBinfeng Lu

❮ Previous
Next ❯

Citations

Jan 11, 2019·Cancers·Alexander David Barrow, Marco Colonna
Feb 14, 2019·Pathology Oncology Research : POR·Miriam Victoria Martín-ManzoJoselin Hernandez
Nov 5, 2019·Nature Reviews. Immunology·Yochai WolfVijay K Kuchroo
Feb 29, 2020·Cells·Itay RaphaelThomas G Forsthuber
May 30, 2020·Cell Research·Xing He, Chenqi Xu
Jul 10, 2020·Cancers·Sachin Kumar Singh ChauhanStephan Kloess
Sep 21, 2018·Frontiers in Immunology·Annika De Sousa LinharesPeter Steinberger
Dec 18, 2018·Frontiers in Immunology·María Pía HolgadoLourdes Arruvito
Aug 9, 2019·Journal of Translational Medicine·Claire CoeshottBrian Nankervis
Nov 9, 2018·Nature Genetics·Karen O DixonVijay K Kuchroo
Aug 21, 2019·Oncoimmunology·Astero KlampatsaSteven M Albelda
Mar 11, 2020·Nature Communications·Michelle SchorerNicole Joller
Aug 24, 2018·Frontiers in Immunology·Anna B MorrisMandy L Ford
Jan 1, 2021·Frontiers in Oncology·Jane KooAlisa B Lee-Sherick
Aug 6, 2019·Trends in Cell Biology·Nicolas CurdyDon-Marc Franchini
Oct 13, 2019·Seminars in Immunology·Walter M KimRichard S Blumberg
Jan 30, 2021·Life Sciences·Nastaran HashemzadehJaleh Barar
Jan 31, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·James J HardingMaria J de Miguel
May 7, 2021·Blood·Sathish K R Padi, Andrew S Kraft
Jun 8, 2021·Cancer Biomarkers : Section a of Disease Markers·Yuting CaoYigang Wang
Aug 7, 2021·The Journal of Biological Chemistry·Rajesh Abraham JacobJimmy D Dikeakos
Jun 24, 2021·Molecular Cancer Therapeutics·Wen-Hsin Sandy LeeCheng-I Wang
Aug 27, 2021·The Biochemical Journal·Courtney M SmithMark A Lemmon

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.