| Autor: |
Miller SD; Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA., Vanderlugt CL, Lenschow DJ, Pope JG, Karandikar NJ, Dal Canto MC, Bluestone JA |
| Jazyk: |
angličtina |
| Zdroj: |
Immunity [Immunity] 1995 Dec; Vol. 3 (6), pp. 739-45. |
| DOI: |
10.1016/1074-7613(95)90063-2 |
| Abstrakt: |
Relapsing experimental autoimmune encephalomyelitis (R-EAE) induced with the immunodominant epitope from proteolipid protein, PLP139-151, is characterized by the development of recurrent relapses with recruitment of T cells reactive to additional myelin peptides, including PLP178-191 (epitope spreading). In this study, we have determined that the CD28/B7 costimulatory pathway is involved in this process. We found preferential up-regulation of B7-1 during the course of R-EAE and a selective increase in its functional costimulatory activity, relative to B7-2. Anti B7-1 F(ab) fragment therapy, but not anti B7-2 MAb therapy, blocked clinical relapses, ameliorated CNS pathology, and blocked epitope spreading. These results suggest that the maintenance of autoimmune reactivity in EAE depends on CD28/B7-1-dependent costimulation of newly recruited T cells responsible for epitope spreading. These studies have important implications for the role of epitope spreading in disease progression and the clinical application of costimulatory antagonists in autoimmune diseases. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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