Glatiramer acetate-reactive T lymphocytes regulate oligodendrocyte progenitor cell number in vitro: role of IGF-2.
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.
Zhang
Y
Y
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Jalili
F
F
Ouamara
N
N
Zameer
A
A
Cosentino
G
G
Mayne
M
M
Hayardeny
L
L
Antel
J P
JP
Bar-Or
A
A
John
G R
GR
D000276:Adjuvants, Immunologic / Q000502:physiology* / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000068717:Glatiramer Acetate; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D018655:Lymphocyte Count / Q000379:methods; D051379:Mice; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010455:Peptides / Q000502:physiology* / Q000627:therapeutic use; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D010455:Peptides; D000068717:Glatiramer Acetate; D007335:Insulin-Like Growth Factor II