Enhanced interferon-gamma-induced Ia-antigen expression by glial cells after previous exposure to this cytokine.
Encephalitogenic T cells appear capable of destroying class II major histocompatibility complex (MHC) antigen (Ia)-positive glial cells in the brain, thus accounting for the pathologic activity of these lymphocytes in experimental autoimmune encephalomyelitis (EAE). However, glial cells do not generally express Ia molecules, suggesting that regulation of Ia expression figures prominently in autoimmune diseases of the central nervous system. In studies to understand the regulatory mechanisms involved in Ia expression, a glial cell clone generated from the brains of neonatal Lewis rats (F10 clone) readily expressed class II major histocompatibility (Ia) antigens after stimulation by interferon-gamma (IFN-gamma) at doses from 10 to 100 units/ml. Level of the antigen decreased gradually within 5-7 days after cultures were depleted of the cytokine. Reexposure of the cells to the IFN-gamma at 100-fold lower doses induced a stronger Ia response than did the initial exposure. F10 cells also expressed Ia when they were cultured with small numbers of syngeneic T lymphocytes, either proliferating or nonproliferating. Proliferating T cells had direct Ia-inducing activity, whereas nonproliferating T cells had this effect only when they were added to cultures with small amounts of T cell-specific antigen. Moreover, Ia-inducing effects of IFN-gamma on F10 cells were also greatly enhanced when these cells were preexposured to T cells. Our results suggest that initial exposure to IFN-gamma or T cells enhances the Ia responsiveness of glial cells to further stimulation with the cytokine.
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Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38101.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000502:physiology
D000906:Antibodies; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma