Measles virus induces apoptosis in uninfected bystander T cells and leads to granzyme B and caspase activation in peripheral blood mononuclear cell cultures.

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  • Author(s): Vuorinen T;Vuorinen T; Peri P; Vainionpää R
  • Source:
    European journal of clinical investigation [Eur J Clin Invest] 2003 May; Vol. 33 (5), pp. 434-42.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Wiley Country of Publication: England NLM ID: 0245331 Publication Model: Print Cited Medium: Print ISSN: 0014-2972 (Print) Linking ISSN: 00142972 NLM ISO Abbreviation: Eur J Clin Invest Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Wiley
      Original Publication: Berlin, New York, Springer-Verlag, on behalf of the European Society for Clinical Investigation.
    • Subject Terms:
      Apoptosis/*immunology ; Caspases/*immunology ; Leukocytes, Mononuclear/*immunology ; Measles virus/*immunology ; Serine Endopeptidases/*immunology; Antigens, CD/immunology ; Blotting, Western ; Cells, Cultured ; Fas Ligand Protein ; Flow Cytometry/methods ; Granzymes ; Humans ; Membrane Glycoproteins/immunology ; Proto-Oncogene Proteins c-bcl-2/immunology ; Receptors, Tumor Necrosis Factor/immunology ; Receptors, Tumor Necrosis Factor, Type I ; T-Lymphocytes/immunology
    • Abstract:
      Background: Measles causes lymphopenia and depresses cell-mediated immunity, but the mechanisms of immunosuppression and cell loss are poorly known.
      Methods: We have used an in vitro model of measles virus (MV)-infected peripheral blood mononuclear cells (PBMCs) and phytohaemagglutinin-stimulated PBMCs in order to assess MV-leucocyte interactions. Cell population undergoing apoptosis was measured by flow cytometry and Annexin-V-fluos staining. The expression of Fas, FasL, TNRF1, and Bcl-2 was analyzed by flow cytometry and Western blotting, and activation of caspase cascade was measured using a colourimetric caspase substrate set. The effects of caspase inhibitors were detected by flow cytometry.
      Results: Measles virus was able to infect monocytes, but interestingly induced apoptosis in uninfected T cells, indicating that induction of apoptosis in T cells is mediated by MV-infected adherent cells. Only 1% of T cells contained MV antigen day 3 p.i. Interestingly the percentage of early apoptotic T cells at the same time was 35%, showing that apoptosis was not the result of MV infection in T cells. Measles virus-induced Fas but not FasL or TNFR1 expression on PMBC, as well as activation of granzyme B and caspase cascade. Simultaneously, overexpression of Bcl-2 protein was detected. Caspase inhibitor decreased the amount of apoptotic T cells.
      Conclusion: Measles virus-infected monocytes induce apoptosis in uninfected T cells, suggesting that infected monocytes probably interact via cell-surface molecules with uninfected T cells and induce apoptosis by indirect mechanisms. Apoptosis of the lymphocytes may contribute to the pathogenesis of MV-induced immunosuppression and cell loss.
    • Accession Number:
      0 (Antigens, CD)
      0 (FASLG protein, human)
      0 (Fas Ligand Protein)
      0 (Membrane Glycoproteins)
      0 (Proto-Oncogene Proteins c-bcl-2)
      0 (Receptors, Tumor Necrosis Factor)
      0 (Receptors, Tumor Necrosis Factor, Type I)
      EC 3.4.21.- (GZMB protein, human)
      EC 3.4.21.- (Granzymes)
      EC 3.4.21.- (Serine Endopeptidases)
      EC 3.4.22.- (Caspases)
    • Publication Date:
      Date Created: 20030426 Date Completed: 20030721 Latest Revision: 20190826
    • Publication Date:
      20231215
    • Accession Number:
      10.1046/j.1365-2362.2003.01164.x
    • Accession Number:
      12713458