Journal article
Multi-Modal Antigen Specific Therapy for Autoimmunity
International reviews of immunology, Vol.20(5), pp.593-611
2001
DOI: 10.3109/08830180109045580
PMID: 11890614
Abstract
Peripheral tolerance, represents an attractive strategy to down-regulate previously activated T cells and suppress an ongoing disease. Herein, immunoglobulins (Igs) were used to deliver self and altered self peptides for efficient peptide presentation without costimulation to test for modulation of experimental allergic encephalomyelitis (EAE). Accordingly, the encephalitogenic proteolipid protein (PLP) sequence 139-151 (referred to as PLP1) and an altered form of PLP1 known as PLP-LR were genetically expressed on Igs and the resulting Ig-PLPl and Ig-PLP-LR were tested for efficient presentation of the peptides and for amelioration of ongoing EAE. Evidence is presented indicating that Ig-PLPl as well as Ig-PLP-LR given in saline to mice with ongoing clinical EAE suppresses subsequent relapses. However, aggregation of both chimeras allows crosslinking of Fcγ receptors (FcγRs) and induction of IL-10 production by APCs but does not promote the up-regulation of costimulatory molecules. Consequently, IL-10 displays bystander suppression and synergizes with presentation without costimulation to drive effective modulation of EAE. As Ig-PLP1 is more potent than Ig-PLP-LR in the down-regulation of T cells, we conclude that peptide affinity plays a critical role in this multi-modal approach of T cell modulation.
Details
- Title: Subtitle
- Multi-Modal Antigen Specific Therapy for Autoimmunity
- Creators
- Kevin L Legge - 1Department of Microbiology, The University of Tennessee, M409 Walters Life Sciences Building, Knoxville, TN, 37996-0845J. Jeremiah Bell - 1Department of Microbiology, The University of Tennessee, M409 Walters Life Sciences Building, Knoxville, TN, 37996-0845Lequn Li - 1Department of Microbiology, The University of Tennessee, M409 Walters Life Sciences Building, Knoxville, TN, 37996-0845Randal Gregg - 1Department of Microbiology, The University of Tennessee, M409 Walters Life Sciences Building, Knoxville, TN, 37996-0845Jacque C Caprio - 1Department of Microbiology, The University of Tennessee, M409 Walters Life Sciences Building, Knoxville, TN, 37996-0845Habib Zaghouani - 1Department of Microbiology, The University of Tennessee, M409 Walters Life Sciences Building, Knoxville, TN, 37996-0845
- Resource Type
- Journal article
- Publication Details
- International reviews of immunology, Vol.20(5), pp.593-611
- Publisher
- Informa UK Ltd
- DOI
- 10.3109/08830180109045580
- PMID
- 11890614
- ISSN
- 0883-0185
- eISSN
- 1563-5244
- Language
- English
- Date published
- 2001
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047749902771
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