The role of CTLA-4 in induction and maintenance of peripheral T cell tolerance

Todd N Eagar; Nitin J Karandikar; Jeffrey A Bluestone; Stephen D Miller

doi:10.1002/1521-4141(200204)32:4<972::AID-IMMU972>3.3.CO;2-D

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The role of CTLA-4 in induction and maintenance of peripheral T cell tolerance

Journal article

Peer reviewed

The role of CTLA-4 in induction and maintenance of peripheral T cell tolerance

Todd N Eagar, Nitin J Karandikar, Jeffrey A Bluestone and Stephen D Miller

European journal of immunology, Vol.32(4), pp.972-981

04/2002

DOI: 10.1002/1521-4141(200204)32:4<972::AID-IMMU972>3.3.CO;2-D

PMID: 11920563

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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.

T-Lymphocyte Subsets - immunology

Antigens, CD - immunology

Myelin Proteolipid Protein - immunology

Ovalbumin - immunology

Encephalomyelitis, Autoimmune, Experimental - immunology

Molecular Sequence Data

Hypersensitivity, Delayed - immunology

B7-2 Antigen

Abatacept

Mice, Mutant Strains

Peptide Fragments - immunology

Female

Receptors, Antigen, T-Cell - immunology

Membrane Glycoproteins - immunology

Cells, Cultured - immunology

Amino Acid Sequence

Antigens, Differentiation - administration & dosage

Immunization

Specific Pathogen-Free Organisms

B7-1 Antigen - immunology

Lymphocyte Activation

Peptide Fragments - administration & dosage

Autoimmune Diseases - immunology

Autoantigens - administration & dosage

Immune Tolerance

Antigens, Differentiation - pharmacology

Inflammation

Myelin Basic Protein - immunology

CTLA-4 Antigen

Capsid - immunology

Encephalomyelitis, Autoimmune, Experimental - therapy

Animals

Thymectomy

Immunoconjugates

Myelin Proteolipid Protein - administration & dosage

Autoantigens - immunology

Capsid Proteins

Autoimmune Diseases - therapy

Clonal Anergy - immunology

Mice

Antigens, Differentiation - immunology

Details

Title: Subtitle: The role of CTLA-4 in induction and maintenance of peripheral T cell tolerance
Creators: Todd N Eagar - Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, IL 60611, USA
Nitin J Karandikar
Jeffrey A Bluestone
Stephen D Miller
Resource Type: Journal article
Publication Details: European journal of immunology, Vol.32(4), pp.972-981
Publisher: Germany
DOI: 10.1002/1521-4141(200204)32:4<972::AID-IMMU972>3.3.CO;2-D
PMID: 11920563
ISSN: 0014-2980
eISSN: 1521-4141
Grant note: NS 34819 / NINDS NIH HHS AI35225 / NIAID NIH HHS NS 30871 / NINDS NIH HHS AI35294 / NIAID NIH HHS CA40216 / NCI NIH HHS NS 26543 / NINDS NIH HHS
Language: English
Date published: 04/2002
Academic Unit: Pathology
Record Identifier: 9984046915202771

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