Journal article
CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis
Journal of neuroimmunology, Vol.109(2), pp.173-180
2000
DOI: 10.1016/S0165-5728(00)00322-2
PMID: 10996219
Abstract
During the progression of relapsing experimental autoimmune encephalomyelitis (R-EAE), in SJL mice, disease relapses are mediated by T cells specific for non-cross-reactive myelin epitopes, a process termed ‘epitope spreading’. CTLA-4, a negative regulator of T cell function modulates R-EAE, in that CTLA-4 blockade exacerbates clinical R-EAE. Herein, we show that CTLA-4-mediated signaling negatively regulates the dynamic spread of autoreactive T cell responses during the course of autoimmune disease. Anti-CTLA-4 mAb, administration at various points during the progression of R-EAE exacerbated subsequent clinical disease and enhanced T cell reactivity to both
inducing and
relapse-associated epitopes. In addition, CTLA-4 blockade during acute disease inhibited clinical remission. Thus, CTLA-4-mediated events are critical for intrinsic regulation of epitope spreading during autoimmune disease.
Details
- Title: Subtitle
- CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis
- Creators
- Nitin J Karandikar - Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USATodd N Eagar - Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USACarol L Vanderlugt - Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USAJeffrey A Bluestone - The Ben May Institute for Cancer Research and the Committee of Immunology, The University of Chicago, Chicago, IL 60637, USAStephen D Miller - Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA
- Resource Type
- Journal article
- Publication Details
- Journal of neuroimmunology, Vol.109(2), pp.173-180
- Publisher
- Elsevier B.V
- DOI
- 10.1016/S0165-5728(00)00322-2
- PMID
- 10996219
- ISSN
- 0165-5728
- eISSN
- 1872-8421
- Language
- English
- Date published
- 2000
- Academic Unit
- Pathology
- Record Identifier
- 9984046817302771
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