More MS news articles for Nov 2001

Pre-emptive targeting of the epitope spreading cascade with genetically modified regulatory T cells during autoimmune demyelinating disease

J Immunol 2001 Dec 1;167(11):6105-12
Yin L, Yu M, Edling AE, Kawczak JA, Mathisen PM, Nanavati T, Johnson JM, Tuohy VK.
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195.

Epitope spreading or endogenous self-priming has been implicated in mediating the progression of autoimmune disease.

In the present study we created an immune-deviated, epitope spreading response in SWXJ mice after the onset of experimental autoimmune encephalomyelitis, a prototypic autoimmune animal model widely used in multiple sclerosis research.

We established an immunoregulatory spreading repertoire by transferring T cells genetically modified to produce high levels of IL-10 in response to a dominant epitope spreading determinant.

Installation of a Th2/Tr1-like spreading repertoire resulted in a marked and prolonged inhibition of disease progression and demyelination characterized by

1) bystander inhibition of the recall response to the priming immunogen, and

2) a Th1-->Tr1 immune-deviated spreading response involving a shift in the source of IL-10 production from the transferred regulatory population to the host-derived, endogenously primed repertoire.

Thus, our data provide a rationale for cell-based therapeutic intervention in multiple sclerosis by showing that pre-emptive targeting of the epitope spreading cascade with regulatory T cells effectively induces an immune-deviated spreading response capable of inhibiting ongoing inflammatory autoreactivity and disease progression.

PMID: 11714769 [PubMed - in process]