Glatiramer acetate (GA) therapy induces a focused, oligoclonal CD8+ T-cell repertoire in multiple sclerosis

Brian W. Biegler, Shirley X. Yan, Sterling B. Ortega, Deepani K. Tennakoon, Michael K. Racke, Nitin J. Karandikar

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

We have demonstrated that GA therapy induces a differential upregulation of GA-specific, cytotoxic/suppressor CD8+ T-cell responses in MS patients. We utilized a novel combination of flow sorting and anchored PCR to analyze the evolving clonal composition of GA-specific CD4+ and CD8+ T-cells. TCRβ chain analysis revealed the development of an oligoclonal GA-specific CD8+ repertoire with persistence of dominant clones over long periods. Interestingly, some sequences resembled published oligoclonal CD8+ TCR sequences from MS lesions. In contrast, GA-specific CD4+ responses were polyclonal and showed continual evolution of their repertoire. This clonotypic and functional analysis provides mechanistic insights into GA therapy.

Original languageEnglish (US)
Pages (from-to)159-171
Number of pages13
JournalJournal of Neuroimmunology
Volume180
Issue number1-2
DOIs
StatePublished - Nov 1 2006

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Keywords

  • CD4
  • CD8
  • Immunotherapy
  • Multiple sclerosis
  • T-cells
  • TCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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