CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis. Academic Article uri icon

Overview

abstract

  • During the progression of relapsing experimental autoimmune encephalomyelitis (R-EAE), in SJL mice, disease relapses are mediated by T cells specific for non-cross-reactive myelin epitopes, a process termed 'epitope spreading'. CTLA-4, a negative regulator of T cell function modulates R-EAE, in that CTLA-4 blockade exacerbates clinical R-EAE. Herein, we show that CTLA-4-mediated signaling negatively regulates the dynamic spread of autoreactive T cell responses during the course of autoimmune disease. Anti-CTLA-4 mAb, administration at various points during the progression of R-EAE exacerbated subsequent clinical disease and enhanced T cell reactivity to both inducing and relapse-associated epitopes. In addition, CTLA-4 blockade during acute disease inhibited clinical remission. Thus, CTLA-4-mediated events are critical for intrinsic regulation of epitope spreading during autoimmune disease.

publication date

  • September 22, 2000

Research

keywords

  • Antigens, Differentiation
  • Encephalomyelitis, Autoimmune, Experimental
  • Epitopes, T-Lymphocyte
  • Immunoconjugates

Identity

Scopus Document Identifier

  • 0034703310

Digital Object Identifier (DOI)

  • 10.1016/s0165-5728(00)00322-2

PubMed ID

  • 10996219

Additional Document Info

volume

  • 109

issue

  • 2