CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis

Nitin J. Karandikar, Todd N. Eagar, Carol L. Vanderlugt, Jeffrey A. Bluestone, Stephen D. Miller

Research output: Contribution to journalArticle

41 Citations (Scopus)

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. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)173-180
Number of pages8
JournalJournal of Neuroimmunology
Volume109
Issue number2
DOIs
StatePublished - Sep 22 2000

Fingerprint

Autoimmune Experimental Encephalomyelitis
Epitopes
Down-Regulation
T-Lymphocytes
Autoimmune Diseases
Recurrence
Acute Disease
Myelin Sheath

Keywords

  • Autoimmunity
  • Costimulation
  • CTLA-4
  • EAE
  • Epitope Spreading

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

Cite this

CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis. / Karandikar, Nitin J.; Eagar, Todd N.; Vanderlugt, Carol L.; Bluestone, Jeffrey A.; Miller, Stephen D.

In: Journal of Neuroimmunology, Vol. 109, No. 2, 22.09.2000, p. 173-180.

Research output: Contribution to journalArticle

Karandikar, Nitin J. ; Eagar, Todd N. ; Vanderlugt, Carol L. ; Bluestone, Jeffrey A. ; Miller, Stephen D. / CTLA-4 downregulates epitope spreading and mediates remission in relapsing experimental autoimmune encephalomyelitis. In: Journal of Neuroimmunology. 2000 ; Vol. 109, No. 2. pp. 173-180.
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