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CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis
- Source :
- Journal of Neuroimmunology. 109:173-180
- Publication Year :
- 2000
- Publisher :
- Elsevier BV, 2000.
-
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.
- Subjects :
- Encephalomyelitis, Autoimmune, Experimental
Immunoconjugates
medicine.drug_class
T-Lymphocytes
T cell
Molecular Sequence Data
Remission, Spontaneous
Immunology
Epitopes, T-Lymphocyte
Mice, Inbred Strains
chemical and pharmacologic phenomena
Cross Reactions
medicine.disease_cause
Monoclonal antibody
Autoantigens
Epitope
Autoimmunity
Abatacept
Mice
Myelin
Multiple Sclerosis, Relapsing-Remitting
Antigens, CD
Recurrence
medicine
Animals
Immunology and Allergy
CTLA-4 Antigen
Hypersensitivity, Delayed
Amino Acid Sequence
Phospholipids
Autoimmune disease
business.industry
Experimental autoimmune encephalomyelitis
Antibodies, Monoclonal
Myelin Basic Protein
hemic and immune systems
Flow Cytometry
medicine.disease
Antigens, Differentiation
Disease Models, Animal
medicine.anatomical_structure
Neurology
CTLA-4
Acute Disease
Immunization
Neurology (clinical)
business
Subjects
Details
- ISSN :
- 01655728
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroimmunology
- Accession number :
- edsair.doi.dedup.....8e466d425259a871280537d622090636