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J Neuroimmunol. 2000 Sep 22;109(2):173-80.

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

Author information

1
Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA.

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.

PMID:
10996219
DOI:
10.1016/s0165-5728(00)00322-2
[Indexed for MEDLINE]

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