[Astrocytes, cells involved in neuro-immune interactions in the central nervous system].
The astrocyte, the major glial cell in the central nervous system, may influence many aspects of inflammation and immune reactivity within the brain. We have established a model of chronically activated T lymphocytes, interacting with neural cells of diverse origin to study the complex immune regulatory system suspected to lead to neuroinflammatory diseases. We show that human astrocytes became reactive following T cell contact, secreting proinflammatory cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinase (TIMP). The altered MMP/TIMP system was shown to be involved in deleterious effects displayed by activated T cells towards human multipotent neural precursers by controlling their sensitivity to T cell-induced Fas-mediated apoptosis. MMP/TIMP was suspected to stabilize Fas at the cell membrane. In a model of mixed rat glial cells in primary culture (astrocytes, oligodendrocytes), activated T lymphocytes induced the collapse of processes and the death of immature oligodendrocytes. These effects were associated with upregulation of Fas at the cell surface of oligodendrocytes and secretion of MMP and TIMP by astrocytes. By amplifying the expression of inflammatory molecules including the MMP/TIMP system, astrocytes appear to be a crucial relay in the deleterious molecular cascade triggered by activated T lymphocytes. Detection of altered MMP/TIMP in patients suffering from myelopathy associated with retroviral infection (HTLV-1) strongly suggests its involvement in the physiopathological process of the disease.
Giraudon
Pascale
P
Inserm U433 Faculté de Médecine R Laënnec, 69372 Lyon. giraudon@lyon.inserm.fr
Malcus
Christophe
C
Chalon
Aurélie
A
Vincent
Peggy
P
Khuth
Seng
S
Bernard
Arlette
A
Belin
Marie-Françoise
MF
D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000502:physiology*; D001921:Brain / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009490:Neurosecretory Systems / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases