Glatiramer acetate-reactive T lymphocytes regulate oligodendrocyte progenitor cell number in vitro: Role of IGF-2

Y. Zhang; F. Jalili; N. Ouamara; A. Zameer; G. Cosentino; M. Mayne; L. Hayardeny; J. P. Antel; A. Bar-Or; G. R. John

doi:10.1016/j.jneuroim.2010.06.014

Glatiramer acetate-reactive T lymphocytes regulate oligodendrocyte progenitor cell number in vitro: Role of IGF-2

Y. Zhang
, F. Jalili
, N. Ouamara
, A. Zameer
, G. Cosentino
, M. Mayne
, L. Hayardeny
, J. P. Antel
, A. Bar-Or
, G. R. John

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Glatiramer acetate (GA) is an immunomodulator approved for therapy of relapsing-remitting multiple sclerosis (RRMS), but recent findings indicate that it may also have additional, neurotrophic effects. Here, we found that supernatants from human GA-reactive T lymphocytes potentiated oligodendrocyte numbers in rodent and human oligodendrocyte progenitor (OPC) cultures. Effects of Th2-polarized lines were stronger than Th1-polarized cells. Microarray and ELISA analyses revealed that neurotrophic factors induced in Th2- and Th1-polarized GA-reactive lines included IGF-2 and BMP-7 respectively, and functional studies confirmed IGF-2 as trophic for OPCs. Our results support the concept that GA therapy may result in supportive effects on oligodendrocytes in RRMS patients.

Original language	English
Pages (from-to)	71-79
Number of pages	9
Journal	Journal of Neuroimmunology
Volume	227
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2010.06.014
State	Published - Oct 2010
Externally published	Yes

Keywords

CNS repair
Glatiramer acetate
Multiple sclerosis
Oligodendrocyte progenitor
T lymphocyte

Access to Document

10.1016/j.jneuroim.2010.06.014

Cite this

@article{e85328a6d5214f249181d60894abff89,

title = "Glatiramer acetate-reactive T lymphocytes regulate oligodendrocyte progenitor cell number in vitro: Role of IGF-2",

abstract = "Glatiramer acetate (GA) is an immunomodulator approved for therapy of relapsing-remitting multiple sclerosis (RRMS), but recent findings indicate that it may also have additional, neurotrophic effects. Here, we found that supernatants from human GA-reactive T lymphocytes potentiated oligodendrocyte numbers in rodent and human oligodendrocyte progenitor (OPC) cultures. Effects of Th2-polarized lines were stronger than Th1-polarized cells. Microarray and ELISA analyses revealed that neurotrophic factors induced in Th2- and Th1-polarized GA-reactive lines included IGF-2 and BMP-7 respectively, and functional studies confirmed IGF-2 as trophic for OPCs. Our results support the concept that GA therapy may result in supportive effects on oligodendrocytes in RRMS patients.",

keywords = "CNS repair, Glatiramer acetate, Multiple sclerosis, Oligodendrocyte progenitor, T lymphocyte",

author = "Y. Zhang and F. Jalili and N. Ouamara and A. Zameer and G. Cosentino and M. Mayne and L. Hayardeny and Antel, \{J. P.\} and A. Bar-Or and John, \{G. R.\}",

note = "Funding Information: The authors thank Dr. Bradford Poulos, Director of the Human Fetal Tissue Repository at the Albert Einstein College of Medicine, for tissue collection, and the Mount Sinai School of Medicine Microscopy Shared Resource Facility. This work was supported by a Research Grant from Teva Pharmaceuticals (GRJ, AB-O, JA), and by National Institutes of Health USPHS Grants NS046620 and NS056074 and ARRA Administrative Supplement NS056074-02S1 (GRJ), and by National Multiple Sclerosis Society Postdoctoral Fellowship FG1739 (YZ) and Research Grant RG3874 (GRJ), and Operating Grant funding through the Canadian Institutes of Health Research (CIHR) New Emerging Team (NET) in Autoimmunity (AB-O) and the Canadian Multiple Sclerosis Society (JA) and Canadian Stem Cell Network (JA), and by the Jayne and Harvey Beker Foundation (GRJ). The MSSM-Microscopy Shared Resource Facility is supported, in part, with funding from the NIH-NCI shared resources grant R24 CA095823. ",

year = "2010",

month = oct,

doi = "10.1016/j.jneuroim.2010.06.014",

language = "English",

volume = "227",

pages = "71--79",

journal = "Journal of Neuroimmunology",

issn = "0165-5728",

publisher = "Elsevier B.V.",

number = "1-2",

}

TY - JOUR

T1 - Glatiramer acetate-reactive T lymphocytes regulate oligodendrocyte progenitor cell number in vitro

T2 - Role of IGF-2

AU - Zhang, Y.

AU - Jalili, F.

AU - Ouamara, N.

AU - Zameer, A.

AU - Cosentino, G.

AU - Mayne, M.

AU - Hayardeny, L.

AU - Antel, J. P.

AU - Bar-Or, A.

AU - John, G. R.

N1 - Funding Information: The authors thank Dr. Bradford Poulos, Director of the Human Fetal Tissue Repository at the Albert Einstein College of Medicine, for tissue collection, and the Mount Sinai School of Medicine Microscopy Shared Resource Facility. This work was supported by a Research Grant from Teva Pharmaceuticals (GRJ, AB-O, JA), and by National Institutes of Health USPHS Grants NS046620 and NS056074 and ARRA Administrative Supplement NS056074-02S1 (GRJ), and by National Multiple Sclerosis Society Postdoctoral Fellowship FG1739 (YZ) and Research Grant RG3874 (GRJ), and Operating Grant funding through the Canadian Institutes of Health Research (CIHR) New Emerging Team (NET) in Autoimmunity (AB-O) and the Canadian Multiple Sclerosis Society (JA) and Canadian Stem Cell Network (JA), and by the Jayne and Harvey Beker Foundation (GRJ). The MSSM-Microscopy Shared Resource Facility is supported, in part, with funding from the NIH-NCI shared resources grant R24 CA095823.

PY - 2010/10

Y1 - 2010/10

N2 - Glatiramer acetate (GA) is an immunomodulator approved for therapy of relapsing-remitting multiple sclerosis (RRMS), but recent findings indicate that it may also have additional, neurotrophic effects. Here, we found that supernatants from human GA-reactive T lymphocytes potentiated oligodendrocyte numbers in rodent and human oligodendrocyte progenitor (OPC) cultures. Effects of Th2-polarized lines were stronger than Th1-polarized cells. Microarray and ELISA analyses revealed that neurotrophic factors induced in Th2- and Th1-polarized GA-reactive lines included IGF-2 and BMP-7 respectively, and functional studies confirmed IGF-2 as trophic for OPCs. Our results support the concept that GA therapy may result in supportive effects on oligodendrocytes in RRMS patients.

AB - Glatiramer acetate (GA) is an immunomodulator approved for therapy of relapsing-remitting multiple sclerosis (RRMS), but recent findings indicate that it may also have additional, neurotrophic effects. Here, we found that supernatants from human GA-reactive T lymphocytes potentiated oligodendrocyte numbers in rodent and human oligodendrocyte progenitor (OPC) cultures. Effects of Th2-polarized lines were stronger than Th1-polarized cells. Microarray and ELISA analyses revealed that neurotrophic factors induced in Th2- and Th1-polarized GA-reactive lines included IGF-2 and BMP-7 respectively, and functional studies confirmed IGF-2 as trophic for OPCs. Our results support the concept that GA therapy may result in supportive effects on oligodendrocytes in RRMS patients.

KW - CNS repair

KW - Glatiramer acetate

KW - Multiple sclerosis

KW - Oligodendrocyte progenitor

KW - T lymphocyte

UR - https://www.scopus.com/pages/publications/77956649226

U2 - 10.1016/j.jneuroim.2010.06.014

DO - 10.1016/j.jneuroim.2010.06.014

M3 - Article

C2 - 20637510

AN - SCOPUS:77956649226

SN - 0165-5728

VL - 227

SP - 71

EP - 79

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

IS - 1-2

ER -

Glatiramer acetate-reactive T lymphocytes regulate oligodendrocyte progenitor cell number in vitro: Role of IGF-2

Abstract

Keywords

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