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

S. D. Miller, C. L. Vanderluat, N. J. Karandikar, J. G. Pope, D. J. Lenschow, M. C. Pal Canto, J. A. Bluestone

Research output: Contribution to journalArticle

Abstract

Immunization of SJL/J mice with the immunodominant epitope on myelin proteolipid protein (PLP139-151) results in a relapsing-remitting form of EAE (REAE). The acute clinical episode of disease is mediated by PLP139-151-specific CD4+ T cells, but the primary relapse is mediated predominantly by T cells specific for a secondary, non-crossreactive PLP epitope (PLP178-191) activated in response to myelin epitopes released during the acute disease episode (I.e., epitope spreading). The CD28/B7 costimulatory pathway is involved in the progression of clinical paralysis in R-EAE following the initial clinical episode. B71 was preferentially upregulated on CNS-resident and infiltrating mononuclear cells during the acute phase of EAE. There was also a selective increase in functional costimulatory activity of B7-1, relative to B7-2, in the splenic APCs from mice, undergoing chronic-relapsing EAE. The critical role of B7-1 in disease progression was highlighted by the ability of and B7-1 F(ab) fragment, but not anti-B7-2 mAb therapy, to effectively block clinical relapses, ameliorate CMS pathology and block epitope spreading when administered during clinical remission. In contrast, injection of intact anti-B7-1 mAb resulted in significant exacerbation of the incidence and severity of clinical relapses, due to its ability to provide costimulation via B7-1 expressed on activated encephalitogenic T cells. These results suggest that the maintenance of autoimmune reactivity in R-EAE depends on CD28/B7-1 -dependent costimulation of naive T cells that are responsible for epitope spreading. (Supported in part by NIH Grants NS30871 andNS34819).

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996

Fingerprint

relapse
epitopes
T-cells
Epitopes
Recurrence
T-lymphocytes
mice
T-Lymphocytes
Myelin Proteolipid Protein
Immunization
Immunodominant Epitopes
myelin proteins
T-Lymphocyte Epitopes
Organized Financing
Acute Disease
Pathology
Myelin Sheath
acute course
Paralysis
myelin sheath

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Miller, S. D., Vanderluat, C. L., Karandikar, N. J., Pope, J. G., Lenschow, D. J., Pal Canto, M. C., & Bluestone, J. A. (1996). Blockade of CD28/B7 interaction prevents epitope spreading and clinical relapses of murine relapsing EAE. FASEB Journal, 10(6).

Blockade of CD28/B7 interaction prevents epitope spreading and clinical relapses of murine relapsing EAE. / Miller, S. D.; Vanderluat, C. L.; Karandikar, N. J.; Pope, J. G.; Lenschow, D. J.; Pal Canto, M. C.; Bluestone, J. A.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

Miller, SD, Vanderluat, CL, Karandikar, NJ, Pope, JG, Lenschow, DJ, Pal Canto, MC & Bluestone, JA 1996, 'Blockade of CD28/B7 interaction prevents epitope spreading and clinical relapses of murine relapsing EAE', FASEB Journal, vol. 10, no. 6.
Miller SD, Vanderluat CL, Karandikar NJ, Pope JG, Lenschow DJ, Pal Canto MC et al. Blockade of CD28/B7 interaction prevents epitope spreading and clinical relapses of murine relapsing EAE. FASEB Journal. 1996;10(6).
Miller, S. D. ; Vanderluat, C. L. ; Karandikar, N. J. ; Pope, J. G. ; Lenschow, D. J. ; Pal Canto, M. C. ; Bluestone, J. A. / Blockade of CD28/B7 interaction prevents epitope spreading and clinical relapses of murine relapsing EAE. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
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