| | |  | | | | Record from Web of Science® | | | | | | |
| T cell receptor peptides in treatment of autoimmune disease: Rationale and potential |
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| Author(s): Vandenbark AA, Hashim GA, Offner H |
| Source: JOURNAL OF NEUROSCIENCE RESEARCH Volume: 43 Issue: 4 Pages: 391-402 Published: FEB 15 1996 |
| Times Cited: 44 References: 86 |
| Abstract: The natural tendency in T cell-mediated autoimmune conditions to develop focused antigen-specific responses that over-utilize certain T cell receptor (TCR) V region segments prompts the induction of anti-TCR-specific T cells and antibodies that can inhibit the pathogenic T cells and promote recovery from disease, This natural regulatory network can be manipulated by injecting synthetic peptide vaccines that correspond to segments of the over-expressed V genes, In experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis (MS), the pathogenic T cells are directed at myelin components, including basic protein (MBP), In some strains such as the Lewis rat and the PL/J mouse, the encephalitogenic BP-specific T cells overexpress a particular V region gene (V beta 8.2) in their TCR, In vivo administration of V beta 8.2 peptides in rats or mice can prevent and treat EAE by boosting regulatory anti-V beta 8.2-specific T cells that inhibit but do not delete the encephalitogenic specificities, This regulation is mediated by soluble factors, suggesting that the presence of regulatory TCR-specific T cells within the target organ (the central nervous system) may inhibit not only the stimulating V beta 8.2+ T cells, but also bystander T cells bearing different V genes, Parallel studies in MS patients have revealed striking V gene biases among BP-specific T cell clones from some patients that provided a rationale for TCR peptide therapy, Injection of V beta 5.2 and V beta 6.1 peptides boosted the frequency of TCR peptide-specific T cells and reduced responses to BP, in some cases with clinical benefit, indicating the presence of an anti-TCR regulatory network in humans that may also be manipulated with TCR peptide therapy. (C) 1996 Wiley-Liss, Inc. |
| Document Type: Review |
| Language: English |
| Reprint Address: Vandenbark, AA (reprint author), VET AFFAIRS MED CTR, NEUROIMMUNOL RES 151D, PORTLAND, OR 97201 USA |
Addresses:
1. OREGON HLTH SCI UNIV, DEPT NEUROL, PORTLAND, OR 97201 USA
2. OREGON HLTH SCI UNIV, DEPT MOLEC MICROBIOL & IMMUNOL, PORTLAND, OR 97201 USA
3. COUNCIL TOBACCO RES, NEW YORK, NY USA |
| Publisher: WILEY-LISS, DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 |
| Subject Category: Neurosciences |
| IDS Number: TY121 |
| ISSN: 0360-4012 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |