The role of CTLA-4 in induction and maintenance of peripheral T cell tolerance
- PMID: 11920563
- DOI: 10.1002/1521-4141(200204)32:4<972::AID-IMMU972>3.0.CO;2-M
The role of CTLA-4 in induction and maintenance of peripheral T cell tolerance
Abstract
T cell receptor engagement and the B7-CD28 / CTLA-4 signaling pathways play critical roles in T cell activation and regulation. CD28 engagement results in T cell activation, differentiation and survival while CTLA-4 signals block IL-2 production, cell cycle progression and T cell differentiation. We explored the role of CTLA-4 in peripheral tolerance induced by intravenous administration of ethylene carbodiimide-fixed, antigen-coupled splenocytes in the PLP139 - 151-induced relapsing experimental autoimmune encephalomyelitis system. Tolerance induction with PLP139 - 151-coupled splenocytes correlates with low B7 expression on the fixed antigen-presenting cells, conditions that would favor CTLA-4-mediated inhibition. Administration of CTLA-4Ig or anti-CTLA-4 concomitant with the 'tolerogenic' stimulus, however, failed to reverse tolerance induction. In contrast, blocking CTLA-4 at the time of secondary 'immunogenic' encounter with antigen reversed the tolerant state. These findings indicate that CTLA-4 is required to maintain the unresponsive state of the tolerized T cells upon antigenic stimulation under inflammatory conditions and, therefore, have important implications for therapeutic regulation of autoimmune disease.
Similar articles
-
Role of the B7-CD28/CTLA-4 pathway in autoimmune disease.Curr Dir Autoimmun. 2002;5:113-30. doi: 10.1159/000060550. Curr Dir Autoimmun. 2002. PMID: 11826754 Review. No abstract available.
-
B7 interactions with CD28 and CTLA-4 control tolerance or induction of mucosal inflammation in chronic experimental colitis.J Immunol. 2001 Aug 1;167(3):1830-8. doi: 10.4049/jimmunol.167.3.1830. J Immunol. 2001. PMID: 11466409
-
The role of CTLA-4 in tolerance induction and ttigen administration cell differentiation in experimental autoimmune encephalomyelitis: i. v. antigen administration.Int Immunol. 1999 Dec;11(12):1889-96. doi: 10.1093/intimm/11.12.1889. Int Immunol. 1999. PMID: 10590254
-
Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis.J Immunol. 2000 Jan 15;164(2):670-8. doi: 10.4049/jimmunol.164.2.670. J Immunol. 2000. PMID: 10623809
-
B7-mediated costimulation can either provoke or prevent clinical manifestations of experimental allergic encephalomyelitis.Immunol Res. 1995;14(3):189-99. doi: 10.1007/BF02918216. Immunol Res. 1995. PMID: 8778209 Review.
Cited by
-
Current and future immunomodulation strategies to restore tolerance in autoimmune diseases.Cold Spring Harb Perspect Biol. 2012 Nov 1;4(11):a007542. doi: 10.1101/cshperspect.a007542. Cold Spring Harb Perspect Biol. 2012. PMID: 23125012 Free PMC article. Review.
-
Tolerance strategies employing antigen-coupled apoptotic cells and carboxylated PLG nanoparticles for the treatment of type 1 diabetes.Rev Diabet Stud. 2012 Winter;9(4):319-27. doi: 10.1900/RDS.2012.9.319. Epub 2012 Dec 28. Rev Diabet Stud. 2012. PMID: 23804269 Free PMC article. Review.
-
Antigen-specific tolerance in immunotherapy of Th2-associated allergic diseases.Crit Rev Immunol. 2013;33(5):389-414. doi: 10.1615/critrevimmunol.2013007046. Crit Rev Immunol. 2013. PMID: 24099300 Free PMC article. Review.
-
Prospects for antigen-specific tolerance based therapies for the treatment of multiple sclerosis.Results Probl Cell Differ. 2010;51:217-35. doi: 10.1007/400_2008_13. Results Probl Cell Differ. 2010. PMID: 19130025 Free PMC article. Review.
-
Predicting Toxicity and Response to Pembrolizumab Through Germline Genomic HLA Class 1 Analysis.JNCI Cancer Spectr. 2020 Dec 29;5(1):pkaa115. doi: 10.1093/jncics/pkaa115. eCollection 2021 Feb. JNCI Cancer Spectr. 2020. PMID: 33554038 Free PMC article. Clinical Trial.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
