Tomkins, Paul Thomas (1989) Interferon modulation of T-cell responses to Semliki Forest virus infected murine brain cells. PhD thesis, University of Warwick.

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Abstract

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.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Library of Congress Subject Headings (LCSH):	Interferon, Immune response -- Regulation, Semliki Forest virus, T cells, Major histocompatibility complex
Official Date:	April 1989
Dates:	Date Event April 1989 Submitted
Institution:	University of Warwick
Theses Department:	Department of Biological Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Morris, A. G. (Alan George)
Sponsors:	Science and Engineering Research Council (Great Britain)
Format of File:	pdf
Extent:	xxi, 272 leaves : illustrations, charts
Language:	eng

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