Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE

• Published in: Immunity (Cambridge, Mass.) Mass.), 1995-12, Vol.3 (6), p.739-745
• Main Authors: Miller, Stephen D., Vanderlugt, Carol L., Lenschow, Deborah J., Pope, Jonathan G., Karandikar, Nitin J., Dal Canto, Mauro C., Bluestone, Jeffrey A.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Blocking - therapeutic use; B7-1 Antigen - immunology; CD28 Antigens - immunology; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Epitopes, T-Lymphocyte - immunology; Female; Mice; Myelin Proteins - immunology; Rats; Recurrence; T-Lymphocytes - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/1074-7613(95)90063-2

Relapsing experimental autoimmune encephalomyelitis (R-EAE) induced with the immunodominant epitope from proteolipid protein, PLP 139–151, is characterized by the development of recurrent relapses with recruitment of T cells reactive to additional myelin peptides, including PLP 179–191 (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.