Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo.
Reactive gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system. To investigate whether soluble factors (cytokines) from inflammatory mononuclear cells that accumulate at lesion sites can provide the cellular signals to initiate gliosis and to identify such cytokines, we have tested and found that supernatants derived from subsets of activated human T lymphocytes (CD8+ or CD4+) are potent mitogens for cultured human adult astrocytes. This effect is blocked by a neutralizing antibody to gamma-interferon (IFN). Recombinant IFN alone can induce proliferation of human adult astrocytes in vitro and increase the extent of trauma-initiated gliosis in the adult mouse brain. The astrocyte proliferation-inducing activity of supernatants of glial cultures treated with IFN can be completely blocked with IFN-neutralizing antibody, suggesting that the proliferative effect does not require intermediary cytokines or cells. These results implicate IFN as an important mediator of the gliosis observed in pathologic conditions of the adult central nervous system associated with infiltrating lymphocytes.
Yong
V W
VW
Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Moumdjian
R
R
Yong
F P
FP
Ruijs
T C
TC
Freedman
M S
MS
Cashman
N
N
Antel
J P
JP
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D009778:Occipital Lobe / Q000502:physiology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D013702:Temporal Lobe / Q000473:pathology
D015703:Antigens, CD; D005904:Glial Fibrillary Acidic Protein; D011994:Recombinant Proteins; D007371:Interferon-gamma