Cbl-b(-/-) T cells demonstrate in vivo resistance to regulatory T cells but a context-dependent resistance to TGF-beta

The Journal of Immunology : Official Journal of the American Association of Immunologists
Catherine O AdamsRobert B Clark

Abstract

Cbl-b is an E3 ubiquitin ligase that negatively regulates T cell activation. Cbl-b(-/-) mice develop spontaneous autoimmunity, and Cbl-b dysregulation has been described in both murine and human autoimmune diseases. Although the mechanisms underlying the development of autoimmunity in Cbl-b(-/-) mice are not yet clear, we have reported that Cbl-b(-/-) CD4(+)CD25(-) effector T cells (Teffs) are resistant to CD4(+)CD25(+) regulatory T cell (Treg)-mediated suppression in vitro and have suggested that this may be an important mechanism in the development of autoimmunity. To confirm the relevance of this resistance to autoimmune disease, we now show that Cbl-b(-/-) Teffs are resistant to suppression by Tregs in vivo and that this involves a resistance of truly naive Cbl-b(-/-) Teffs. Additionally, we show that Cbl-b(-/-) Tregs are fully functional in vivo, further suggesting that the regulatory abnormalities in Cbl-b(-/-) mice are related to defects in Teff, not Treg, function. To characterize the relevance of TGF-beta sensitivity in Treg resistance, we examined in vivo Th17 generation and report that Cbl-b(-/-) mice are able to mount a normal Th17 response in vivo. As Cbl-b(-/-) Teffs have been shown to be insensitive to the suppre...Continue Reading

References

Oct 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·H Y TseT H Hansen
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qizhi TangJeffrey A Bluestone
May 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Angela M ThorntonEthan M Shevach
Jul 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elizabeth A WohlfertRobert B Clark
Aug 17, 2004·Immunity·Myung-Shin JeonJosef M Penninger
Mar 9, 2005·The Journal of Experimental Medicine·Linda FahlénFiona Powrie
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elizabeth A WohlfertRobert B Clark
May 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Zhi ChenJohn J O'Shea
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yutaka KomiyamaYoichiro Iwakura
Mar 17, 2007·Immunity·Arian LaurenceJohn J O'shea
Mar 17, 2007·The Journal of Clinical Investigation·Jeffrey Y ChiangHua Gu
Apr 4, 2007·The Journal of Experimental Medicine·Stefanie LoeserJosef M Penninger
Nov 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jaeseok YangNick D Jones
Mar 7, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kentaro TanakaAkihiko Yoshimura
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anya SchneiderJane H Buckner
Jun 19, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hongwei QinYingzi Cong
Oct 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie-Clare St RoseAdam J Adler
Mar 23, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ling LuSong Guo Zheng

❮ Previous
Next ❯

Citations

Mar 9, 2011·Immunology and Cell Biology·Christina Lutz-NicoladoniDominik Wolf
May 28, 2013·Journal of Molecular Cell Biology·Thomas GruberGottfried Baier
Jun 23, 2012·Open Biology·Mazin A Al-SalihiGopal P Sapkota
Feb 18, 2012·Upsala Journal of Medical Sciences·Miriam De Boeck, Peter ten Dijke
Mar 31, 2015·Frontiers in Oncology·Christina Lutz-NicoladoniSieghart Sopper
Jun 1, 2016·Frontiers in Immunology·Emily R Mercadante, Ulrike M Lorenz
Feb 2, 2017·International Journal of Molecular Sciences·Agnieszka Kempinska-PodhorodeckaPiotr Milkiewicz
Nov 25, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Gwilym J Webb, David H Adams
Apr 30, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Fan Pan, Joseph Barbi
Jun 15, 2017·Oncotarget·Sebastian PeerThomas Gruber
Apr 15, 2011·Immunological Reviews·Dilan DissanayakePamela S Ohashi
Feb 12, 2017·Frontiers in Immunology·Mai FujiwaraRobert B Clark
Nov 8, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Charles W TranPamela S Ohashi
Oct 24, 2018·Frontiers in Immunology·Sebastian PeerThomas Gruber
Aug 10, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emily J AnstadtRobert B Clark
May 7, 2019·Frontiers in Oncology·SeongJun HanPamela S Ohashi
Dec 12, 2020·Clinical and Experimental Immunology·D JafariA Esmaeilzadeh
Jan 4, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiaoli HuXueqiong Zhu

❮ 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.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Related Papers

The Journal of Immunology : Official Journal of the American Association of Immunologists
Elizabeth A WohlfertRobert B Clark
The Journal of Immunology : Official Journal of the American Association of Immunologists
Elizabeth A WohlfertRobert B Clark
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae
Jie GaoJi-ye Zhu
© 2021 Meta ULC. All rights reserved