Anti-CTLA-4 antibody treatment triggers determinant spreading and enhances murine myasthenia gravis

The Journal of Immunology : Official Journal of the American Association of Immunologists
H B WangH G Ljunggren

Abstract

CTLA-4 appears to be a negative regulator of T cell activation and is implicated in T cell-mediated autoimmune diseases. Experimental autoimmune myasthenia gravis (EAMG), induced by immunization of C57BL/6 mice with acetylcholine receptor (AChR) in adjuvant, is an autoantibody-mediated disease model for human myasthenia gravis (MG). The production of anti-AChR Abs in MG and EAMG is T cell dependent. In the present study, we demonstrate that anti-CTLA-4 Ab treatment enhances T cell responses to AChR, increases anti-AChR Ab production, and provokes a rapid onset and severe EAMG. To address possible mechanisms underlying the enhanced autoreactive T cell responses after anti-CTLA-4 Ab treatment, mice were immunized with the immunodominant peptide alpha(146-162) representing an extracellular sequence of the ACHR: Anti-CTLA-4 Ab, but not control Ab, treatment subsequent to peptide immunization results in clinical EAMG with diversification of the autoantibody repertoire as well as enhanced T cell proliferation against not only the immunizing alpha(146-162) peptide, but also against other subdominant epitopes. Thus, treatment with anti-CTLA-4 Ab appears to induce determinant spreading, diversify the autoantibody repertoire, and enhance...Continue Reading

References

Oct 1, 1990·The Journal of Clinical Investigation·B S PrabhakarA L Notkins
Jan 1, 1981·Methods in Enzymology·J LindstromS Tzartos
Jan 1, 1980·The Journal of Experimental Medicine·P W Berman, J Patrick
May 1, 1993·Immunology Today·P V LehmannG Gammon
Aug 1, 1994·Immunity·T L WalunasJ A Bluestone
Jun 23, 1994·The New England Journal of Medicine·D B Drachman
Mar 22, 1996·Science·D R LeachJ P Allison
Aug 1, 1996·The Journal of Experimental Medicine·N J KarandikarJ A Bluestone
May 1, 1995·Annals of Neurology·R A LewisR P Lisak
Oct 1, 1996·Immunological Reviews·P WaterhouseT W Mak
Jul 21, 1997·The Journal of Experimental Medicine·K McCoyG L Gros
Mar 21, 1998·The Journal of Experimental Medicine·F LühderD Mathis
Jun 25, 1998·Current Opinion in Immunology·T Saito
Jul 21, 1998·Annals of the New York Academy of Sciences·B M Conti-FineZ Y Wang
Jan 23, 1999·Current Opinion in Immunology·D Mason, F Powrie
Apr 26, 2000·Clinical Immunology : the Official Journal of the Clinical Immunology Society·H B WangH Link
Mar 23, 2001·Nature Immunology·F D ShiH G Ljunggren

❮ Previous
Next ❯

Citations

Aug 29, 2002·Clinical and Experimental Immunology·E A WatermanA P Weetman
May 20, 2003·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·F Harding
Dec 13, 2012·Expert Opinion on Therapeutic Targets·Katja Simon-KellerAlexander Marx
Apr 2, 2014·Investigational New Drugs·Hassane IzzedinePhilippe Rouvier
May 5, 2016·Nature Reviews. Clinical Oncology·Celine BoutrosCaroline Robert
Nov 28, 2018·Annals of Clinical and Translational Neurology·Koutaro TakamatsuYukio Ando
Sep 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Richard J DiPaolo, Emil R Unanue
Mar 26, 2002·Nature Reviews. Immunology·Carol L Vanderlugt, Stephen D Miller
Aug 5, 2009·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Gary HunterChristopher A Robinson
Sep 2, 2015·The Journal of Clinical Investigation·Lieping Chen, Xue Han
Jun 28, 2018·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Eda Derle, Sibel Benli
Aug 18, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·F D ShiN Sarvetnick
Oct 29, 2014·Journal for Immunotherapy of Cancer·Chrisann KyiMichael A Postow
Dec 21, 2012·Annals of the New York Academy of Sciences·Erdem TüzünPremkumar Christadoss
Jun 21, 2012·Cancer Immunology, Immunotherapy : CII·Connie JackamanDelia J Nelson
Sep 2, 2016·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Motoya Mie, Takeshi Takahashi
Oct 9, 2015·Case Reports in Oncological Medicine·Diwakar DavarJohn M Kirkwood
Jan 27, 2018·Expert Review of Vaccines·William S BowenHaval Shirwan
May 19, 2020·The International Journal of Neuroscience·Zhan-Xia XueXue-Liang Wu
May 20, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kimberly E BeckJames C Yang
May 21, 2015·American Society of Clinical Oncology Educational Book·Michael A Postow
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tibor KelerAlan Korman
Apr 30, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Douglas B JohnsonJeffrey A Sosman
May 10, 2020·Journal of Cellular Physiology·Abbas HajifathaliMajid Gholizadeh
May 3, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Peter Brossart
Feb 7, 2021·Immunology and Cell Biology·Chun-Ting J KwongBalasubramanian Krishnamurthy
Apr 3, 2020·Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society·Katherine J Williams, Richard C Allen
Sep 16, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J NaidooJ D Wolchok

❮ 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.