CTLA-4 expressed by FOXP3+ regulatory T cells prevents inflammatory tissue attack and not T-cell priming in arthritis

Immunology
Katrin KlockeKajsa Wing

Abstract

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) -mediated regulation of already tolerized autoreactive T cells is critical for understanding autoimmune responses. Although defects in CTLA-4 contribute to abnormal FOXP3+ regulatory T (Treg) cell function in rheumatoid arthritis, its role in autoreactive T cells remains elusive. We studied immunity towards the dominant collagen type II (CII) T-cell epitope in collagen-induced arthritis both in the heterologous setting and in the autologous setting where CII is mutated at position E266D in mouse cartilage. CTLA-4 regulated all stages of arthritis, including the chronic phase, and affected the priming of autologous but not heterologous CII-reactive T cells. CTLA-4 expression by both conventional T (Tconv) cells and Treg cells was required but while Tconv cell expression was needed to control the priming of naive autoreactive T cells, CTLA-4 on Treg cells prevented the inflammatory tissue attack. This identifies a cell-type-specific time window when CTLA-4-mediated tolerance is most powerful, which has important implications for clinical therapy with immune modulatory drugs.

References

Aug 1, 1992·The Journal of Experimental Medicine·L MoriM Steinmetz
Apr 30, 1996·Proceedings of the National Academy of Sciences of the United States of America·V MalmströmR Holmdahl
Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·F LuhderD Mathis
Jun 1, 2002·Ageing Research Reviews·Rikard HolmdahlHisakata Yamada
Oct 9, 2002·Nature Immunology·Ursula GrohmannPaolo Puccetti
Nov 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lucy S K WalkerAbul K Abbas
May 15, 2003·Arthritis and Rheumatism·Mary E MorganRené E M Toes
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Johan BäcklundRikard Holmdahl
Jul 29, 2004·The Journal of Experimental Medicine·Michael R EhrensteinClaudia Mauri
May 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alexandra P TreschowShohreh Issazadeh-Navikas
Jun 30, 2005·Arthritis and Rheumatism·Mary E MorganRené E M Toes
Feb 1, 2007·Arthritis and Rheumatism·Linh T NguyenChristophe Benoist
Jan 22, 2008·Annals of the Rheumatic Diseases·R AxmannG Schett
Oct 11, 2008·Science·Kajsa WingShimon Sakaguchi
Nov 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Fabian Flores-BorjaMichael R Ehrenstein
May 12, 2009·Immunological Reviews·Christopher E RuddHelga Schneider
May 31, 2011·Autoimmunity Reviews·Makoto MiyaraZahir Amoura
Jul 5, 2011·Trends in Immunology·Kajsa WingShimon Sakaguchi
Dec 14, 2011·The New England Journal of Medicine·Iain B McInnes, Georg Schett
May 15, 2012·Swiss Medical Weekly·Johannes von KempisPeter M Villiger
Jul 4, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chun Jing WangLucy S K Walker
Jul 4, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emily Corse, James P Allison
Jul 20, 2014·Cancer Immunology Research·Tsvetelina Pentcheva-HoangJames P Allison
Oct 29, 2014·Journal for Immunotherapy of Cancer·Chrisann KyiMichael A Postow
Dec 24, 2014·Immunology and Cell Biology·Dean FranckaertSusan M Schlenner
Jan 15, 2015·Trends in Immunology·Lucy S K Walker, David M Sansom
Apr 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Katrin KlockeKajsa Wing

❮ Previous
Next ❯

Citations

Dec 12, 2017·Frontiers in Immunology·Hai ZhaoYan Kang
Sep 3, 2019·Frontiers in Immunology·Annelies DemeyerRudi Beyaert
Dec 24, 2018·Nature Communications·Leonie BrockmannSamuel Huber
Dec 19, 2020·International Journal of Molecular Sciences·Myun Soo KimDaeho Cho
Jan 26, 2021·Biochemistry and Biophysics Reports·Yuki FujiharaHiroshi Nishiura
Mar 6, 2021·STAR Protocols·Ioannis SkordosRudi Beyaert

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Related Papers

The Journal of Immunology : Official Journal of the American Association of Immunologists
Alexandra TreschowShohreh Issazadeh-Navikas
European Journal of Immunology
Roberto SpreaficoSalvatore Albani
Transplant International : Official Journal of the European Society for Organ Transplantation
Dela Golshayan
© 2022 Meta ULC. All rights reserved