Cultures of astrocytes prepared from the brains of newborn mice, G26-24 oligodendroglioma cells and C1300 neuroblastoma cells were treated with Interferon (IFN) and the effect on major histocompatibility complex (MHC) antigen expression assessed by indirect immunofluorescence. IFN-αβ increased class I, but not class II, MHC antigen expression on astrocytes, G26-24 cells and C1300 cells. IFN-β1, increased class I, but not class II, MHC antigen expression on astrocytes. IFN-γ increased both class I and class II MHC antigen expression on astrocytes and G26-24 cells. IFN-γ increased class I, but not class II, MHC antigen expression on C1300 cells. IFN-αβ and IFN-β were additive with IFN-γ in the induction of class I MHC antigen expression on astrocytes, but inhibited the ability of IFN-γ to induce class II MHC antigen expression. IFN-αβ and IFN-γ increased the susceptibility of astrocytes, C26-24 cells and C1300 cells to lysis by alloreactive cytotoxic T-lymphocytes (CTL) indicating that IFNs increased the ability of the cells to participate in class I MHC restricted T-cell immune reactions. Astrocytes treated with IFN-αβ or IFN-γ, and G26-24 cells and C1300 cells treated with IFN-γ, prior to infection with Semliki Forest virus (SFV), showed a similar or increased susceptibility to SFV-specific CTL lysis, despite a reduction of SFV antigen display on the cells, as assessed by indirect immunofluorescence and susceptibility to lysis by anti-SFV antibody plus complement. It is concluded that even when SFV antigen expression is reduced by IFN treatment, in the context of enhanced class I MHC antigen expression cells remain susceptible to SFV-specific CTL lysis. IFN-αβ and IFN-γ treatment of astrocytes, and IFN-γ treatment of G26-24 cells, prior to treatment with a β-propiolactone inactivated preparation of SFV, increased the ability of the cells to stimulate SFV-specific T-cell release of IFN-γ. This increased ability correlated with an increase in MHC antigen expression on the cells. IFN-γ released by SFV-specific T-cells increased class I and class II MHC antigen expression on astrocytes and G26-24 cells indicating that a positive feedback mechanism could operate. SFV-infected newborn and adult mice possessed high levels of IFN-αβ in the brain. Brain extracts prepared from SFV-infected newborn and adult mice increased class I, but not class II, MHC antigen expression on astrocytes in vitro. Class I and class II MHC antigen expression was slightly elevated in the brains of SFV-infected newborn mice. To study the role of endogenous IFN-γ, R4-6A2 anti-IFN-γ monoclonal antibody was administered to adult mice, prior to infection with SFV, and the effect on the clinical course of SFV-disease monitored. R4- 6A2 antibody had no effect and preliminary experiments indicated that the antibody may not neutralise all IFN-γ activity in vivo under the conditions used.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:237061 |
| Date | January 1989 |
| Creators | Tomkins, Paul Thomas |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/101165/ |
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