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

doi:10.1016/j.jneuroim.2006.07.015

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

Journal article

Peer reviewed

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 and Nitin J Karandikar

Journal of neuroimmunology, Vol.180(1), pp.159-171

2006

DOI: 10.1016/j.jneuroim.2006.07.015

PMID: 16935352

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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.

T-cells

Multiple sclerosis

TCR

CD4

Immunotherapy

CD8

Details

Title: Subtitle: Glatiramer acetate (GA) therapy induces a focused, oligoclonal CD8+ T-cell repertoire in multiple sclerosis
Creators: Brian W Biegler - Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Shirley X Yan - Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Sterling B Ortega - Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Deepani K Tennakoon - Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Michael K Racke - Department of Neurology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Nitin J Karandikar - Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Resource Type: Journal article
Publication Details: Journal of neuroimmunology, Vol.180(1), pp.159-171
Publisher: Elsevier B.V
DOI: 10.1016/j.jneuroim.2006.07.015
PMID: 16935352
ISSN: 0165-5728
eISSN: 1872-8421
Language: English
Date published: 2006
Academic Unit: Pathology
Record Identifier: 9984046900402771

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