Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE

Stephen D Miller; Carol L Vanderlugt; Deborah J Lenschow; Jonathan G Pope; Nitin J Karandikar; Mauro C Dal Canto; Jeffrey A Bluestone

doi:10.1016/1074-7613(95)90063-2

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Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE

Journal article

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Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE

Stephen D Miller, Carol L Vanderlugt, Deborah J Lenschow, Jonathan G Pope, Nitin J Karandikar, Mauro C Dal Canto and Jeffrey A Bluestone

Immunity (Cambridge, Mass.), Vol.3(6), pp.739-745

1995

DOI: 10.1016/1074-7613(95)90063-2

PMID: 8777719

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Abstract

Relapsing experimental autoimmune encephalomyelitis (R-EAE) induced with the immunodominant epitope from proteolipid protein, PLP 139–151, is characterized by the development of recurrent relapses with recruitment of T cells reactive to additional myelin peptides, including PLP 179–191 (epitope spreading). In this study, we have determined that the CD28/B7 costimulatory pathway is involved in this process. We found preferential up-regulation of B7-1 during the course of R-EAE and a selective increase in its functional costimulatory activity, relative to B7-2. Anti B7-1 F(ab) fragment therapy, but not anti B7-2 MAb therapy, blocked clinical relapses, ameliorated CNS pathology, and blocked epitope spreading. These results suggest that the maintenance of autoimmune reactivity in EAE depends on CD28/B7-1-dependent costimulation of newly recruited T cells responsible for epitope spreading. These studies have important implications for the role of epitope spreading in disease progression and the clinical application of costimulatory antagonists in autoimmune diseases.

Details

Title: Subtitle: Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE
Creators: Stephen D Miller - Department of Microbiology-Immunology, USA
Carol L Vanderlugt - Department of Microbiology-Immunology, USA
Deborah J Lenschow - Department of Pathology Interdepartmental Immunobiology Center Northwestern University Medical School Chicago, Illinois, 60611, USA
Jonathan G Pope - Department of Microbiology-Immunology, USA
Nitin J Karandikar - Department of Microbiology-Immunology, USA
Mauro C Dal Canto - The Ben May Institute and the Committee of Immunology The University of Chicago Chicago, Illinois 60637, USA
Jeffrey A Bluestone - Department of Pathology Interdepartmental Immunobiology Center Northwestern University Medical School Chicago, Illinois, 60611, USA
Resource Type: Journal article
Publication Details: Immunity (Cambridge, Mass.), Vol.3(6), pp.739-745
Publisher: Elsevier Inc
DOI: 10.1016/1074-7613(95)90063-2
PMID: 8777719
ISSN: 1074-7613
eISSN: 1097-4180
Language: English
Date published: 1995
Academic Unit: Pathology
Record Identifier: 9984047982402771

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