Treatment with intact anti-B7-1 mAb during disease remission enhances epitope spreading and exacerbates relapses in R-EAE

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

doi:10.1016/S0165-5728(97)00108-2

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Treatment with intact anti-B7-1 mAb during disease remission enhances epitope spreading and exacerbates relapses in R-EAE

Journal article

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Treatment with intact anti-B7-1 mAb during disease remission enhances epitope spreading and exacerbates relapses in R-EAE

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

Journal of neuroimmunology, Vol.79(2), pp.113-118

1997

DOI: 10.1016/S0165-5728(97)00108-2

PMID: 9394783

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Abstract

PLP139–151-induced experimental autoimmune encephalomyelitis in the SJL mouse is a Th1-mediated inflammatory demyelinating disease characterized by a relapsing–remitting clinical course (R-EAE). Clinical relapses are mediated by T cells specific for a non-cross reactive secondary PLP epitope (PLP178–191) induced by epitope spreading. We have previously shown that B7-1 expression is upregulated in SJL mice undergoing R-EAE and in vivo treatment during remission with F(ab) fragments of anti-B7-1 mAb, blocked epitope spreading and disease progression. In contrast, the present study shows that treatment with intact anti-B7-1 mAb exacerbated clinical disease relapses and enhanced CNS demyelination. Anti-B7-1-treated mice showed enhanced in vivo delayed-type hypersensitivity (DTH) to the relapse-associated PLP178–191 epitope and responses to the immunodominant MBP84–104 epitope which are absent in the controls. Thus, ligation of B7-1 by intact mAbs has effects opposite to those of anti-B7-1 F(ab) fragments suggesting that the mAb is directly signaling through B7-1 expressed on T cells and/or APCs.

Experimental autoimmune encephalomyelitis

T cell costimulation

Epitope spreading

SJL/J mice

B7-1

Proteolipid protein

Details

Title: Subtitle: Treatment with intact anti-B7-1 mAb during disease remission enhances epitope spreading and exacerbates relapses in R-EAE
Creators: Carol L Vanderlugt - Department of Microbiology–Immunology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA
Nitin J Karandikar - Department of Microbiology–Immunology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA
Deborah J Lenschow - The Ben May Institute for Cancer Research and the Committee of Immunology, The University of Chicago, Chicago, IL 60637, USA
Mauro C Dal Canto - Department of Pathology and Interdepartmental Immunobiology Center, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA
Jeffrey A Bluestone - The Ben May Institute for Cancer Research and the Committee of Immunology, The University of Chicago, Chicago, IL 60637, USA
Stephen D Miller - Department of Microbiology–Immunology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA
Resource Type: Journal article
Publication Details: Journal of neuroimmunology, Vol.79(2), pp.113-118
Publisher: Elsevier B.V
DOI: 10.1016/S0165-5728(97)00108-2
PMID: 9394783
ISSN: 0165-5728
eISSN: 1872-8421
Language: English
Date published: 1997
Academic Unit: Pathology
Record Identifier: 9984047643202771

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