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

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 journal › Article › peer-review

27 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 language	English
Pages (from-to)	159-171
Number of pages	13
Journal	Journal of Neuroimmunology
Volume	180
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2006.07.015
State	Published - Nov 2006

Keywords

CD4
CD8
Immunotherapy
Multiple sclerosis
T-cells
TCR

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10.1016/j.jneuroim.2006.07.015

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@article{4584143547ce4c1a9c1d93912b2cc017,

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

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.",

keywords = "CD4, CD8, Immunotherapy, Multiple sclerosis, T-cells, TCR",

author = "Biegler, {Brian W.} and Yan, {Shirley X.} and Ortega, {Sterling B.} and Tennakoon, {Deepani K.} and Racke, {Michael K.} and Karandikar, {Nitin J.}",

note = "Funding Information: These studies were supported, in part, by the following research grant awards: NJK: USPHS NIH grant AI53439 and the National MS Society Grant JF2118-A-2 and MKR: NIH grants NS37513, AI47133, NS044250 and The National MS Society Grant RG2969-B-7. NJK is a Harry Weaver Neuroscience Scholar of the National MS Society. The authors would like to thank Becky Price, RN, for performing the leukapheresis and Bonnie Darnell for technical assistance with cell sorting. ",

year = "2006",

month = nov,

doi = "10.1016/j.jneuroim.2006.07.015",

language = "English",

volume = "180",

pages = "159--171",

journal = "Journal of Neuroimmunology",

issn = "0165-5728",

publisher = "Elsevier",

number = "1-2",

}

TY - JOUR

T1 - Glatiramer acetate (GA) therapy induces a focused, oligoclonal CD8+ T-cell repertoire in multiple sclerosis

AU - Biegler, Brian W.

AU - Yan, Shirley X.

AU - Ortega, Sterling B.

AU - Tennakoon, Deepani K.

AU - Racke, Michael K.

AU - Karandikar, Nitin J.

N1 - Funding Information: These studies were supported, in part, by the following research grant awards: NJK: USPHS NIH grant AI53439 and the National MS Society Grant JF2118-A-2 and MKR: NIH grants NS37513, AI47133, NS044250 and The National MS Society Grant RG2969-B-7. NJK is a Harry Weaver Neuroscience Scholar of the National MS Society. The authors would like to thank Becky Price, RN, for performing the leukapheresis and Bonnie Darnell for technical assistance with cell sorting.

PY - 2006/11

Y1 - 2006/11

N2 - 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.

AB - 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.

KW - CD4

KW - CD8

KW - Immunotherapy

KW - Multiple sclerosis

KW - T-cells

KW - TCR

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U2 - 10.1016/j.jneuroim.2006.07.015

DO - 10.1016/j.jneuroim.2006.07.015

M3 - Article

C2 - 16935352

AN - SCOPUS:33750628251

SN - 0165-5728

VL - 180

SP - 159

EP - 171

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

IS - 1-2

ER -

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

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Keywords

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